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1. Previous immune checkpoint inhibitor therapy is associated with decreased COVID-19-related hospitalizations and complications in patients with cancer: Results of a propensity-matched analysis of the OnCovid registry

Author: Anahita Mostaghim, Samuel Minkove, Juan Aguilar-Company, Isabel Ruiz-Camps, Simeon Eremiev-Eremiev, Gino M. Dettorre, Laura Fox, Carlo Tondini, Joan Brunet, MCarmen Carmona-García, Matteo Lambertini, Mark Bower, Thomas Newsom-Davis, Rachel Sharkey, Alessia Dalla Pria, Maura Rossi, Andrea Plaja, Ramon Salazar, Anna Sureda, Aleix Prat, Vasiliki Michalarea, Mieke Van Hemelrijck, Ailsa Sita-Lumsden, Alexia Bertuzzi, Lorenza Rimassa, Sabrina Rossi, Gianpiero Rizzo, Paolo Pedrazzoli, Alvin JX Lee, Cian Murphy, Katherine Belessiotis, Nikolaos Diamantis, Uma Mukherjee, Fanny Pommeret, Annabelle Stoclin, Clara Martinez-Vila, Riccardo Bruna, Gianluca Gaidano, Francesca D'Avanzo, Alessandra Gennari, Janhavi Athale, Peter Eichacker, David J. Pinato, Parizad Torabi-Parizi, and Alessio Cortellini
Subjects: COVID-19, SARS-CoV-2, Malignancy, Immunotherapy, Checkpoint inhibitor, Infectious and parasitic diseases, RC109-216
Abstract: Objectives: To date, studies have not provided definitive answers regarding whether previous immune checkpoint inhibitor (ICI) treatment alters outcomes for cancer patients with COVID-19. Methods: The OnCovid registry (NCT04393974) was searched from February 27, 2020, to January 31, 2022, for patients who received systemic anti-cancer therapy in the 4 weeks before laboratory-confirmed COVID-19 diagnosis. Propensity-score matching using country, vaccination status, primary tumor type, sex, age, comorbidity burden, tumor stage, and remission status investigated differences in predefined clinical outcomes comparing those who had or had not received ICIs. Results: Of 3523 patients screened, 137 ICI-only and 1378 non-ICI met inclusion criteria. Before matching, ICI patients were older, male, enrolled at centers in Italy, and had histories of smoking, thoracic cancers, advanced cancer stages, and active malignancies (P ≤0.02). After matching, there were 120 ICI and 322 non-ICI patients. ICI patients had no differences (odds ratio: 95% CI) in presenting COVID-19 symptoms (0.69: 0.37-1.28), receipt of COVID-specific therapy (0.88: 0.54-1.41), 14-day (0.95: 0.56-1.61), or 28-day (0.79: 0.48-1.29) mortalities. However, ICI patients required less COVID-19-related hospitalization (0.37: 0.21-0.67) and oxygen therapy (0.51: 0.31-0.83) and developed fewer complications (0.57: 0.36-0.92). Conclusion: In this propensity-score matched analysis, previous ICI therapy did not worsen and potentially improved COVID-19 outcomes in patients with cancer.
Published: 2024
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2. Immunomodulators for immunocompromised patients hospitalized for COVID-19: a meta-analysis of randomized controlled trialsResearch in context

Author: Ilias I. Siempos, Andre C. Kalil, Drifa Belhadi, Viviane Cordeiro Veiga, Alexandre Biasi Cavalcanti, Westyn Branch-Elliman, Eleni Papoutsi, Konstantinos Gkirgkiris, Nikoleta A. Xixi, Anastasia Kotanidou, Olivier Hermine, Raphaël Porcher, Xavier Mariette, Philippe Ravaud, Serge Bureau, Maxime Dougados, Matthieu Resche-Rigon, Pierre-Louis Tharaux, Annick Tibi, Elie Azoulay, Jacques Cadranel, Joseph Emmerich, Muriel Fartoukh, Bertrand Guidet, Marc Humbert, Karine Lacombe, Matthieu Mahevas, Frédéric Pene, Valerie Pourchet-Martinez, Frédéric Schlemmer, Yazdan Yazdanpanah, Gabriel Baron, Elodie Perrodeau, Damien Vanhoye, Cécile Kedzia, Lauren Demerville, Anne Gysembergh-Houal, Alexandre Bourgoin, Nabil Raked, Lakhdar Mameri, Claire Montlahuc, Lucie Biard, St.phanie Alary, Samir Hamiria, Thinhinane Bariz, Hala Semri, Dhiaa Meriem Hai, Moustafa Benafla, Mohamed Belloul, Pernelle Vauboin, Saskia Flamand, Claire Pacheco, Anouk Walter-Petrich, Emilia Stan, Souad Benarab, Corine Nyanou, Robin Charreteur, Céline Dupre, Kévin Cardet, Blandine Lehmann, Kamyl Baghli, Claire Madelaine, Eric D'Ortenzio, Oriane Puéchal, Caroline Semaille, Laurent Savale, Anatole Harrois, Samy Figueiredo, Jacques Duranteau, Nadia Anguel, Arthur Pavot, Xavier Monnet, Christian Richard, Jean-Louis Teboul, Philippe Durand, Pierre Tissieres, Mitja Jevnikar, David Montani, Stephan Pavy, Gaétane Nocturne, Samuel Bitoun, Nicolas Noel, Olivier Lambotte, Lelia Escaut, Stephane Jauréguiberry, Elodie Baudry, Christiane Verny, Edouard Lefevre, Mohamad Zaidan, Domitille Molinari, Gaël Leprun, Alain Fourreau, Laurent Cylly, Lamiae Grimaldi, Myriam Virlouvet, Ramdane Meftali, Soléne Fabre, Marion Licois, Asmaa Mamoune, Yacine Boudali, Clotilde Le Tiec, Céline Verstuyft, Anne-Marie Roques, Sophie Georgin-Lavialle, Patricia Senet, Gilles Pialoux, Angele Soria, Antoine Parrot, Helene François, Nathalie Rozensztajn, Emmanuelle Blin, Pascaline Choinier, Juliette Camuset, Jean-Simon Rech, Antony Canellas, Camille Rolland-Debord, Nadege Lemarié, Nicolas Belaube, Marine Nadal, Martin Siguier, Camille Petit-Hoang, Julie Chas, Elodie Drouet, Matthieu Lemoine, Audrey Phibel, Lucie Aunay, Eliane Bertrand, Sylviane Ravato, Marie Vayssettes, Anne Adda, Celine Wilpotte, Pélagie Thibaut, Julie Fillon, Isabelle Debrix, Soraya Fellahi, Jean-Philippe Bastard, Guillaume Lefévre, Jacques-Eric Gottenberg, Yves Hansmann, Frédéric Blanc, Sophie Ohlmann-Caillard, Vincent Castelain, Emmanuel Chatelus, Eva Chatron, Olivier Collange, François Danion, Frédéric De Blay, Pierre Diemunsch, Sophie Diemunsch, Renaud Felten, Bernard Goichot, Valentin Greigert, Aurelien Guffroy, Bob Heger, Charlotte Kaeuffer, Loic Kassegne, Anne Sophie Korganow, Pierrick Le Borgne, Nicolas Lefebvre, Paul-Michel Mertes, Eric Noll, Mathieu Oberlin, Vincent Poindron, Julien Pottecher, Yvon Ruch, François Weill, Nicolas Meyer, Emmanuel Andres, Eric Demonsant, Hakim Tayebi, Gabriel Nisand, Stéphane Brin, Cédric Sublon, Guillaume Becker, Anne Hutt, Tristan Martin, Sophie Bayer, Catherine Metzger, Arsene Mekinian, Noémie Abisror, Amir Adedjouma, Diane Bollens, Marion Bonneton, Nathalie Bourcicaux, Anne Bourrier, Maria Chauchard Thibault Chiarabiani, Doroth.e Chopin, Jonathan Cohen, Ines Devred, Bruno Donadille, Olivier Fain, Geoffrey Hariri, Vincent Jachiet, Patrick Ingliz, Marc Garnier, Marc Gatfosse, Etienne Ghrenassia, Delphine Gobert, Jessica Krause le Garrec, Cecilia Landman, Jean Remy Lavillegrand, Benedicte Lefebvre, Thibault Mahevas, Sandie Mazerand, Jean Luc Meynard, Marjolaine Morgand, Zineb Ouaz.ne, Jerome Pacanowski, S.bastien Riviere, Philippe Seksik, Harry Sokol, Heithem Soliman, Nadia Valin, Thomas Urbina, Chloé McAvoy, Maria Pereira Miranda, Gladys Aratus, Laurence Berard, Tabassome Simon, Anne Daguenel Nguyen, Elise Girault, Cl.mentine Mayala-Kanda, Marie Antignac, Céline Leplay, Jean-Benoit Arlet, Jean-Luc Diehl, Florence Bellenfant, Anne Blanchard, Alexandre Buffet, Bernard Cholley, Antoine Fayol, Edouard Flamarion, Anne Godier, Thomas Gorget, Sophie-Rym Hamada, Caroline Hauw-Berlemont, Jean-Sébastien Hulot, David Lebeaux, Marine Livrozet, Adrien Michon, Arthur Neuschwander, Marie-Aude Pennet, Benjamin Planquette, Brigitte Ranque, Olivier Sanchez, Geoffroy Volle, Sandrine Briois, Mathias Cornic, Virginie Elisee, Jesuthasan Denis, Juliette Djadi-Prat, Pauline Jouany, Ramon Junquera, Mickael Henriques, Amina Kebir, Isabelle Lehir, Jeanne Meunier, Florence Patin, Val.rie Paquet, Anne Tréhan, Véronique Vigna, Brigitte Sabatier, Damien Bergerot, Charléne Jouve, Camille Knosp, Olivia Lenoir, Nassim Mahtal, Léa Resmini, Xavier Lescure, Jade Ghosn, Antoine Bachelard, Anne Rachline, Valentina Isernia, Bao-chau, Phung, Dorothée Vallois, Aurelie Sautereau, Catherine Neukrich, Antoine Dossier, Raphaël Borie, Bruno Crestani, Gregory Ducrocq, Philippe Gabriel Steg, Philippe Dieude, Thomas Papo, Estelle Marcault, Marhaba Chaudhry, Charléne Da Silveira, Annabelle Metois, Ismahan Mahenni, Meriam Meziani, Cyndie Nilusmas, Sylvie Le Gac, Awa Ndiaye, Fran.oise Louni, Malikhone Chansombat, Zelie Julia, Solaya Chalal, Lynda Chalal, Laura Kramer, Jeniffer Le Grand, Kafif Ouifiya, Valentine Piquard, Sarah Tubiana, Yann Nguyen, Vasco Honsel, Emmanuel Weiss, Anais Codorniu, Virginie Zarrouk, Victoire de Lastours, Matthieu Uzzan, Naura Gamany, Agathe Claveirole, Alexandre Navid, Tiffanie Fouque, Yonathan Cohen, Maya Lupo, Constance Gilles, Roza Rahli, Zeina Louis, David Boutboul, Lionel Galicier, Yaël Amara, Gabrielle Archer, Amira Benattia, Anne Bergeron, Louise Bondeelle, Nathalie de Castro, Melissa Clément, Michaël Darmon, Blandine Denis, Clairelyne Dupin, Elsa Feredj, Delphine Feyeux, Adrien Joseph, Etienne Lenglin, Pierre Le Guen, Geoffroy Liégeon, Gwenaël Lorillon, Asma Mabrouki, Eric Mariotte, Grégoire Martin de Frémont, Adrien Mirouse, Jean-Michel Molina, Régis Peffault de Latour, Eric Oksenhendler, Julien Saussereau, Abdellatif Tazi, Jean-Jacques Tudesq, Lara Zafrani, Isabelle Brindele, Emmanuelle Bugnet, Karine Celli Lebras, Julien Chabert, Lamia Djaghout, Catherine Fauvaux, Anne Lise Jegu, Ewa Kozakiewicz, Martine Meunier, Marie-Thérèse Tremorin, Claire Davoine, Isabelle Madelaine, Sophie Caillat-Zucman, Constance Delaugerre, Florence Morin, Damien Sène, Ruxandra Burlacu, Benjamin Chousterman, Bruno Mégarbanne, Pascal Richette, Jean-Pierre Riveline, Aline Frazier, Eric Vicaut, Laure Berton, Tassadit Hadjam, Miguel Alejandro Vazquez-Ibarra, Clément Jourdaine, Olivia Tran, Véronique Jouis, Aude Jacob, Julie Smati, Stéphane Renaud, Claire Pernin, Lydia Suarez, Luca Semerano, Sébastien Abad, Ruben B. nainous, Nicolas Bonnet, Celine Comparon, Yves Cohen, Hugues Cordel, Robin Dhote, Nathalie Dournon, Boris Duchemann, Nathan Ebstein, Thomas Gille, Benedicte Giroux-Leprieur, Jeanne Goupil de Bouille, Hilario Nunes, Johanna Oziel, Dominique Roulot, Lucile Sese, ClaireTantet, Yurdagul Uzunhan, Coralie Bloch-Queyrat, Vincent Levy, Fadhila Messani, Mohammed Rahaoui, Myléne Petit, Sabrina Brahmi, Vanessa Rathoin, Marthe Rigal, Nathalie Costedoat-Chalumeau, Liem Binh Luong, Zakaria Ait Hamou, Sarah Benghanem, Philippe Blanche, Nicolas Carlier, Benjamin Chaigne, Remy Gauzit, Hassan Joumaa, Mathieu Jozwiak, Marie Lachétre, Hélène Lafoeste, Odie Launay, Paul Legendre, Jonathan Marey, Caroline Morbieu, Lola-Jade Palmieri, Tali-Anne Szwebel, Hendy Abdoul, Alexandra Bruneau, Audrey Beclin-Clabaux, Charly Larrieu, Pierre Montanari, Eric Dufour, Ada Clarke, Catherine Le Bourlout, Nathalie Marin, Nathalie Menage, Samira Saleh-Mghir, Mamadou Salif Cisse, Kahina Cheref, Corinne Guerin, Jérémie Zerbit, Marc Michel, Sébastien Gallien, Etienne Crickx, Benjamin Le Vavasseur, Emmanuelle Kempf, Karim Jaffal, William Vindrios, Julie Oniszczuk, Constance Guillaud, Pascal Lim, Elena Fois, Giovanna Melica, Marie Matignon, Maud Jalabert, Jean-Daniel Lelièvre, David Schmitz, Marion Bourhis, Sylia Belazouz, Laetitia Languille, Caroline Boucle, Nelly Cita, Agnés Didier, Fahem Froura, Katia Ledudal, Thiziri Sadaoui, Alaki Thiemele, Delphine Le Febvre De Bailly, Muriel Carvhalo Verlinde, Julien Mayaux, Patrice Cacoub, David Saadoun, Mathieu Vautier, Héléne Bugaut, Olivier Benveniste, Yves Allenbach, Gaëlle Leroux, Aude Rigolet, Perrine Guillaume-Jugnot, Fanny Domont, Anne Claire Desbois, Chloé Comarmond, Nicolas Champtiaux, Segolene Toquet, Amine Ghembaza, Matheus Vieira, Georgina Maalouf, Goncalo Boleto, Yasmina Ferfar, Jean-Christophe Corvol, C.line Louapre, Sara Sambin, Louise-Laure Mariani, Carine Karachi, Florence Tubach, Candice Estellat, Linda Gimeno, Karine Martin, Aicha Bah, Vixra Keo, Sabrine Ouamri, Yasmine Messaoudi, Nessima Yelles, Pierre Faye, Sebastien Cavelot, Cecile Larcheveque, Laurence Annonay, Jaouad Benhida, Aida Zahrate-Ghoul, Soumeya Hammal, Ridha Belilita, Fanny Charbonnier, Claire Aguilar, Fanny Alby-Laurent, Carole Burger, Clara Campos-Vega, Nathalie Chavarot, Benjamin Fournier, Claire Rouzaud, Damien Vimpére, Caroline Elie, Prissile Bakouboula, Laure Choupeaux, Sophie Granville, Elodie Issorat, Christine Broissand, Marie-Alexandra Alyanakian, Guillaume Geri, Nawal Derridj, Naima Sguiouar, Hakim Meddah, Mourad Djadel, Héléne Chambrin-Lauvray, Jean-Charles Duclos-vallée, Faouzi Saliba, Sophie-Caroline Sacleux, Ilias Kounis, Sonia Tamazirt, Eric Rudant, Jean-Marie Michot, Annabelle Stoclin, Emeline Colomba, Fanny Pommeret, Christophe Willekens, Rosa Da Silva, Valérie Dejean, Yasmina Mekid, Ines Ben-Mabrouk, Florence Netzer, Caroline Pradon, Laurence Drouard, Valérie Camara-Clayette, Alexandre Morel, Gilles Garcia, Abolfazl Mohebbi, Férial Berbour, Mélanie Dehais, Anne-Lise Pouliquen, Alison Klasen, Loren Soyez-Herkert, Jonathan London, Younes Keroumi, Emmanuelle Guillot, Guillaume Grailles, Younes El amine, Fanny Defrancq, Hanane Fodil, Chaouki Bouras, Dominique Dautel, Nicolas Gambier, Thierno Dieye, Boris Bienvenu, Victor Lancon, Laurence Lecomte, Kristina Beziriganyan, Belkacem Asselate, Laure Allanic, Elena Kiouris, Marie-Héléne Legros, Christine Lemagner, Pascal Martel, Vincent Provitolo, Félix Ackermann, Mathilde Le Marchand, Aurélie Chan Hew Wai, Dimitri Fremont, Elisabeth Coupez, Mireille Adda, Frédéric Duée, Lise Bernard, Antoine Gros, Estelle Henry, Claire Courtin, Anne Pattyn, Pierre-Grégoire Guinot, Marc Bardou, Agnes Maurer, Julie Jambon, Amélie Cransac, Corinne Pernot, Bruno Mourvillier, Eric Marquis, Philippe Benoit, Damien Roux, Coralie Gernez, Cécile Yelnik, Julien Poissy, Mandy Nizard, Fanette Denies, Helene Gros, Jean-Jacques Mourad, Emmanuelle Sacco, Sophie Renet, F. Ader, Y. Yazdanpanah, F. Mentre, N. Peiffer-Smadja, F.X. Lescure, J. Poissy, L. Bouadma, J.F. Timsit, B. Lina, F. Morfin-Sherpa, M. Bouscambert, A. Gaymard, G. Peytavin, L. Abel, J. Guedj, C. Andrejak, C. Burdet, C. Laouenan, D. Belhadi, A. Dupont, T. Alfaiate, B. Basli, A. Chair, S. Laribi, J. Level, M. Schneider, M.C. Tellier, A. Dechanet, D. Costagliola, B. Terrier, M. Ohana, S. Couffin-Cadiergues, H. Esperou, C. Delmas, J. Saillard, C. Fougerou, L. Moinot, L. Wittkop, C. Cagnot, S. Le Mestre, D. Lebrasseur-Longuet, V. Petrov-Sanchez, A. Diallo, N. Mercier, V. Icard, B. Leveau, S. Tubiana, B. Hamze, A. Gelley, M. Noret, E. D’Ortenzio, O. Puechal, C. Semaille, T. Welte, J.A. Paiva, M. Halanova, M.P. Kieny, E. Balssa, C. Birkle, S. Gibowski, E. Landry, A. Le Goff, L. Moachon, C. Moins, L. Wadouachi, C. Paul, A. Levier, D. Bougon, F. Djossou, L. Epelboin, J. Dellamonica, C.H. Marquette, C. Robert, S. Gibot, E. Senneville, V. Jean-Michel, Y. Zerbib, C. Chirouze, A. Boyer, C. Cazanave, D. Gruson, D. Malvy, P. Andreu, J.P. Quenot, N. Terzi, K. Faure, C. Chabartier, V. Le Moing, K. Klouche, T. Ferry, F, Valour, B. Gaborit, E. Canet, P. Le Turnier, D. Boutoille, F. Bani-Sadr, F. Benezit, M. Revest, C. Cameli, A. Caro, MJ Ngo Um Tegue, Y. Le Tulzo, B. Laviolle, F. Laine, G. Thiery, F. Meziani, Y. Hansmann, W. Oulehri, C. Tacquard, F. Vardon-Bounes, B. Riu-Poulenc, M. Murris-Espin, L. Bernard, D. Garot, O. Hinschberger, M. Martinot, C. Bruel, B. Pilmis, O. Bouchaud, P. Loubet, C. Roger, X. Monnet, S. Figueiredo, V. Godard, J.P. Mira, M. Lachatre, S. Kerneis, J. Aboab, N. Sayre, F. Crockett, D. Lebeaux, A. Buffet, J.L. Diehl, A. Fayol, J.S. Hulot, M. Livrozet, A Mekontso- Dessap, C. Ficko, F. Stefan, J. Le Pavec, J. Mayaux, H. Ait-Oufella, J.M. Molina, G. Pialoux, M. Fartoukh, J. Textoris, M. Brossard, A. Essat, E. Netzer, Y. Riault, M. Ghislain, L. Beniguel, M. Genin, L. Gouichiche, C. Betard, L. Belkhir, A. Altdorfer, V Fraipont Centro, S. Braz, JM Ferreira Ribeiro, R Roncon Alburqueque, M. Berna, M. Alexandre, B. Lamprecht, A. Egle, R. Greil, M. Joannidis, Thomas F. Patterson, Philip O. Ponce, Barbara S. Taylor, Jan E. Patterson, Jason E. Bowling, Heta Javeri, LuAnn Larson, Angela Hewlett, Aneesh K. Mehta, Nadine G. Rouphael, Youssef Saklawi, Nicholas Scanlon, Jessica J. Traenkner, Ronald P. Trible, Jr., Emmanuel B. Walter, Noel Ivey, Thomas L. Holland, Guillermo M. Ruiz-Palacios, Alfredo Ponce de León, Sandra Rajme, Lanny Hsieh, Alpesh N. Amin, Miki Watanabe, Helen S. Lee, Susan Kline, Joanne Billings, Brooke Noren, Hyun Kim, Tyler D. Bold, Victor Tapson, Jonathan Grein, Fayyaz Sutterwala, Nicole Iovine, Lars K. Beattie, Rebecca Murray Wakeman, Matthew Shaw, Mamta K. Jain, Satish Mocherla, Jessica Meisner, Amneris Luque, Daniel A. Sweeney, Constance A. Benson, Farhana Ali, Robert L. Atmar, Hana M. El Sahly, Jennifer Whitaker, Ann R. Falsey, Angela R. Branche, Cheryl Rozario, Justino Regalado Pineda, José Arturo Martinez-Orozco, David Chien Lye, Sean WX. Ong, Po Ying Chia, Barnaby E. Young, Uriel Sandkovsky, Mezgebe Berhe, Clinton Haley, Emma Dishner, Valeria D. Cantos, Colleen F. Kelley, Paulina A. Rebolledo Esteinou, Sheetal Kandiah, Sarah B. Doernberg, Pierre-Cedric B. Crouch, Hannah Jang, Anne F. Luetkemeyer, Jay Dwyer, Stuart H. Cohen, George R. Thompson, 3rd, Hien H. Nguyen, Robert W. Finberg, Jennifer P. Wang, Juan Perez-Velazquez, Mireya Wessolossky, Patrick E.H. Jackson, Taison D. Bell, Miranda J. West, Babafemi Taiwo, Karen Krueger, Johnny Perez, Triniece Pearson, Catharine I. Paules, Kathleen G. Julian, Danish Ahmad, Alexander G. Hajduczok, Henry Arguinchona, Christa Arguinchona, Nathaniel Erdmann, Paul Goepfert, Neera Ahuja, Maria G. Frank, David Wyles, Heather Young, Myoung-don Oh, Wan Beom Park, Chang Kyung Kang, Vincent Marconi, Abeer Moanna, Sushma Cribbs, Telisha Harrison, Eu Suk Kim, Jongtak Jung, Kyoung-Ho Song, Hong Bin Kim, Seow Yen Tan, Humaira Shafi, MF Jaime Chien, Raymond KC. Fong, Daniel D. Murray, Jens Lundgren, Henrik Nielsen, Tomas Jensen, Barry S. Zingman, Robert Grossberg, Paul F. Riska, Otto O. Yang, Jenny Ahn, Rubi Arias, Rekha R. Rapaka, Naomi Hauser, James D. Campbell, William R. Short, Pablo Tebas, Jillian T. Baron, Susan L.F. McLellan, Lucas S. Blanton, Justin B. Seashore, C. Buddy Creech, Todd W. Rice, Shannon Walker, Isaac P. Thomsen, Diego Lopez de Castilla, Jason W. Van Winkle, Francis X. Riedo, Surinder Kaur Pada, Alvin DY. Wang, Li Lin, Michelle Harkins, Gregory Mertz, Nestor Sosa, Louis Yi Ann Chai, Paul Anantharajah Tambyah, Sai Meng Tham, Sophia Archuleta, Gabriel Yan, David A. Lindholm, Ana Elizabeth Markelz, Katrin Mende, Richard Mularski, Elizabeth Hohmann, Mariam Torres-Soto, Nikolaus Jilg, Ryan C. Maves, Gregory C. Utz, Sarah L. George, Daniel F. Hoft, James D. Brien, Roger Paredes, Lourdes Mateu, Cora Loste, Princy Kumar, Sarah Thornton, Sharmila Mohanraj, Noreen A. Hynes, Lauren M. Sauer, Christopher J. Colombo, Christina Schofield, Rhonda E. Colombo, Susan E. Chambers, Richard M. Novak, Andrea Wendrow, Samir K. Gupta, Tida Lee, Tahaniyat Lalani, Mark Holodniy, Aarthi Chary, Nikhil Huprikar, Anuradha Ganesan, Norio Ohmagari, Ayako Mikami, D. Ashley Price, Christopher J.A. Duncan, Kerry Dierberg, Henry J. Neumann, Stephanie N. Taylor, Alisha Lacour, Najy Masri, Edwin Swiatlo, Kyle Widmer, James D. Neaton, Mary Bessesen, David S. Stephens, Timothy H. Burgess, Timothy M. Uyeki, Robert Walker, G. Lynn Marks, Anu Osinusi, Huyen Cao, Anabela Cardoso, Stephanie de Bono, Douglas E. Schlichting, Kevin K. Chung, Jennifer L. Ferreira, Michelle Green, Mat Makowski, Michael R. Wierzbicki, Tom M. Conrad, Jill Ann El-Khorazaty, Heather Hill, Tyler Bonnett, Nikki Gettinger, Theresa Engel, Teri Lewis, Jing Wang, John H. Beigel, Kay M. Tomashek, Varduhi Ghazaryan, Tatiana Beresnev, Seema Nayak, Lori E. Dodd, Walla Dempsey, Effie Nomicos, Marina Lee, Rhonda Pikaart-Tautges, Mohamed Elsafy, Robert Jurao, Hyung Koo, Michael Proschan, Tammy Yokum, Janice Arega, Ruth Florese, Jocelyn D. Voell, Richard Davey, Ruth C. Serrano, Zanthia Wiley, Varun K. Phadke, Paul A. Goepfert, Carlos A. Gomez, Theresa A. Sofarelli, Laura Certain, Hannah N. Imlay, Cameron R. Wolfe, Emily R. Ko, John J. Engemann, Nora Bautista Felix, Claire R. Wan, Sammy T. Elmor, Laurel R. Bristow, Michelle S. Harkins, Nicole M. Iovine, Marie-Carmelle Elie-Turenne, Victor F. Tapson, Pyoeng Gyun Choe, Richard A. Mularski, Kevin S. Rhie, Rezhan H. Hussein, Dilek Ince, Patricia L. Winokur, Jin Takasaki, Sho Saito, Kimberly McConnell, PharmD, David L. Wyles, Ellen Sarcone, Kevin A. Grimes, Katherine Perez, Charles Janak, Jennifer A. Whitaker, Paulina A. Rebolledo, John Gharbin, Allison A. Lambert, Diego F. Zea, Emma Bainbridge, David C. Hostler, Jordanna M. Hostler, Brian T. Shahan, Evelyn Ling, Minjoung Go, Fleesie A. Hubbard, Melony Chakrabarty, Maryrose Laguio-Vila, Edward E. Walsh, Faheem Guirgis, Vincent C. Marconi, Christian Madar, Scott A. Borgetti, Corri Levine, Joy Nock, Keith Candiotti, Julia Rozman, Fernando Dangond, Yann Hyvert, Andrea Seitzinger, Kaitlyn Cross, Stephanie Pettibone, Seema U. Nayak, and Gregory A. Deye
Subjects: Acute respiratory distress syndrome, Acute hypoxemic respiratory failure, Pneumonia, Critically ill, Cancer, Medicine (General), R5-920
Abstract: Summary: Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61–1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64–1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09–0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.
Published: 2024
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3. Impact of SARS-CoV-2 vaccines and recent chemotherapy on COVID-19 morbidity and mortality in patients with soft tissue sarcoma: an analysis from the OnCovid registry

Author: Bruno Vincenzi, Alessio Cortellini, Alessandro Mazzocca, Sarah Orlando, Davide Romandini, Juan Aguilar-Company, Isabel Ruiz-Camps, Claudia Valverde Morales, Simeon Eremiev-Eremiev, Carlo Tondini, Joan Brunet, Rossella Bertulli, Salvatore Provenzano, Mark Bower, Daniele Generali, Ramon Salazar, Anna Sureda, Aleix Prat, Michalarea Vasiliki, Mieke Van Hemelrijck, Ailsa Sita-Lumsden, Alexia Bertuzzi, Sabrina Rossi, Amanda Jackson, Federica Grosso, Alvin J. X. Lee, Cian Murphy, Katherine Belessiotis, Uma Mukherjee, Fanny Pommeret, Angela Loizidou, Gianluca Gaidano, Gino M. Dettorre, Salvatore Grisanti, Marco Tucci, Claudia A. M. Fulgenzi, Alessandra Gennari, Andrea Napolitano, and David J. Pinato
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Background: To date, limited evidence exists on the impact of COVID-19 in patients with soft tissue sarcoma (STS), nor about the impact of SARS-CoV-2 vaccines and recent chemotherapy on COVID-19 morbidity and mortality in this specific population. Methods: We described COVID-19 morbidity and mortality among patients with STS across ‘Omicron’ (15 December 2021–31 January 2022), ‘Pre-vaccination’ (27 February 2020–30 November 2020), and ‘Alpha-Delta’ phase (01 December 2020–14 December 2021) using OnCovid registry participants (NCT04393974). Case fatality rate at 28 days (CFR 28 ) and COVID-19 severity were also described according to the SARS-CoV-2 vaccination status, while the impact of the receipt of cytotoxic chemotherapy within 4 weeks prior to COVID-19 on clinical outcomes was assessed with Inverse Probability of Treatment Weighting (IPTW) models adjusted for possible confounders. Results: Out of 3820 patients, 97 patients with STS were included. The median age at COVID-19 diagnosis was 56 years (range: 18–92), with 65 patients (67%) aged < 65 years and most patients had a low comorbidity burden (65, 67.0%). The most frequent primary tumor sites were the abdomen (56.7%) and the gynecological tract (12.4%). In total, 36 (37.1%) patients were on cytotoxic chemotherapy within 4 weeks prior to COVID-19. The overall CFR 28 was 25.8%, with 38% oxygen therapy requirement, 34% rate of complications, and 32.3% of hospitalizations due to COVID-19. CFR 28 (29.5%, 21.4%, and 12.5%) and all indicators of COVID-19 severity demonstrated a trend toward a numerical improvement across the pandemic phases. Similarly, vaccinated patients demonstrated numerically improved CFR 28 (16.7% versus 27.7%) and COVID-19 morbidity compared with unvaccinated patients. Patients who were on chemotherapy experienced comparable CFR 28 (19.4% versus 26.0%, p = 0.4803), hospitalizations (50.0% versus 44.4%, p = 0.6883), complication rates (30.6% versus 34.0%, p = 0.7381), and oxygen therapy requirement (28.1% versus 40.0%, p = 0.2755) compared to those who were not on anticancer therapy at COVID-19, findings further confirmed by the IPTW-fitted multivariable analysis. Conclusion: In this study, we demonstrate an improvement in COVID-19 outcomes in patients with STS over time. Recent exposure to chemotherapy does not impact COVID-19 morbidity and mortality and SARS-CoV-2 vaccination confers protection against adverse outcomes from COVID-19 in this patient population.
Published: 2024
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4. Use of covid-19 convalescent plasma to treat patients admitted to hospital for covid-19 with or without underlying immunodeficiency: open label, randomised clinical trial

Author: Arsène Mekinian, Xavier Mariette, Florence Ader, Raphaël Porcher, Philippe Ravaud, Lionel Piroth, Gabriel Baron, Jean-Marie Michot, Karine Lacombe, Tabassome Simon, Sophie Georgin-Lavialle, Charles Cazanave, Marc Michel, Olivier Hermine, Guillaume Martin-Blondel, Fabrice Bonnet, Pierre Tiberghien, Xavier Lescure, Xavier de Lamballerie, Valérie Pourcher, Matthieu Resche-Rigon, Thibault Chiarabini, Stella Rousset, Fanny Pommeret, Thomas Hueso, Julien Saison, Nathalie De Castro, Anne Francois, Pascal Morel, Nora Soussi, Phillipe Brun, Pierre Sellier, and Pierre-Louis Tharaux
Subjects: Medicine
Abstract: Objective To evaluate the efficacy of covid-19 convalescent plasma to treat patients admitted to hospital for moderate covid-19 disease with or without underlying immunodeficiency (CORIPLASM trial).Design Open label, randomised clinical trial.Setting CORIMUNO-19 cohort (publicly supported platform of open label, randomised controlled trials of immune modulatory drugs in patients admitted to hospital with moderate or severe covid-19 disease) based on 19 university and general hospitals across France, from 16 April 2020 to 21 April 2021.Participants 120 adults (n=60 in the covid-19 convalescent plasma group, n=60 in the usual care group) admitted to hospital with a positive SARS-CoV2 test result, duration of symptoms 40.Main outcome measures Primary outcomes were proportion of patients with a WHO Clinical Progression Scale score of ≥6 on the 10 point scale on day 4 (higher values indicate a worse outcome), and survival without assisted ventilation or additional immunomodulatory treatment by day 14. Secondary outcomes were changes in WHO Clinical Progression Scale scores, overall survival, time to discharge, and time to end of dependence on oxygen supply. Predefined subgroups analyses included immunosuppression status, duration of symptoms before randomisation, and use of steroids.Results 120 patients were recruited and assigned to covid-19 convalescent plasma (n=60) or usual care (n=60), including 22 (covid-19 convalescent plasma) and 27 (usual care) patients who were immunocompromised. 13 (22%) patients who received convalescent plasma had a WHO Clinical Progression Scale score of ≥6 at day 4 versus eight (13%) patients who received usual care (adjusted odds ratio 1.88, 95% credible interval 0.71 to 5.24). By day 14, 19 (31.6%) patients in the convalescent plasma group and 20 (33.3%) patients in the usual care group needed ventilation, additional immunomodulatory treatment, or had died. For cumulative incidence of death, three (5%) patients in the convalescent plasma group and eight (13%) in the usual care group died by day 14 (adjusted hazard ratio 0.40, 95% confidence interval 0.10 to 1.53), and seven (12%) patients in the convalescent plasma group and 12 (20%) in the usual care group by day 28 (adjusted hazard ratio 0.51, 0.20 to 1.32). In a subgroup analysis performed in patients who were immunocompromised, transfusion of covid-19 convalescent plasma was associated with mortality (hazard ratio 0.39, 95% confidence interval 0.14 to 1.10).Conclusions In this study, covid-19 convalescent plasma did not improve early outcomes in patients with moderate covid-19 disease. The efficacy of convalescent plasma in patients who are immunocompromised should be investigated further.Trial registration ClinicalTrials.gov NCT04345991.
Published: 2023
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5. Correction: Metabolomic analyses of COVID-19 patients unravel stage-dependent and prognostic biomarkers

Author: François-Xavier Danlos, Claudia Grajeda-Iglesias, Sylvère Durand, Allan Sauvat, Mathilde Roumier, Delphine Cantin, Emeline Colomba, Julien Rohmer, Fanny Pommeret, Giulia Baciarello, Christophe Willekens, Marc Vasse, Frank Griscelli, Jean-Eudes Fahrner, Anne-Gaëlle Goubet, Agathe Dubuisson, Lisa Derosa, Nitharsshini Nirmalathasan, Delphine Bredel, Séverine Mouraud, Caroline Pradon, Annabelle Stoclin, Flore Rozenberg, Jérôme Duchemin, Georges Jourdi, Syrine Ellouze, Françoise Levavasseur, Laurence Albigès, Jean-Charles Soria, Fabrice Barlesi, Eric Solary, Fabrice André, Frédéric Pène, Félix Ackerman, Luc Mouthon, Laurence Zitvogel, Aurélien Marabelle, Jean-Marie Michot, Michaela Fontenay, and Guido Kroemer
Subjects: Cytology, QH573-671
Published: 2024
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6. Immune checkpoint inhibitor therapy and outcomes from SARS-CoV-2 infection in patients with cancer: a joint analysis of OnCovid and ESMO-CoCARE registries

Author: Joan Brunet, Josep Tabernero, Salvatore Grisanti, Matteo Lambertini, George Pentheroudakis, Bruno Vincenzi, Dirk Arnold, Juan Aguilar-Company, Paolo Pedrazzoli, Solange Peters, Luis Castelo-Branco, Emanuela Romano, Olivier Michielin, Ramon Salazar, Alessio Cortellini, Rossana Berardi, Aleix Prat, Spyridon Gennatas, Giuseppe Tonini, Urania Dafni, Kevin J Harrington, Paola Queirolo, David J Pinato, Francesca Mazzoni, David Viñal, Gino M Dettorre, Uma Mukherjee, Mark Bower, Alexia Bertuzzi, Ailsa Sita-Lumsden, Federica Biello, Andrea Patriarca, Alessandra Gennari, Maura Rossi, Zoi Tsourti, Vasileios Angelis, Jacobo Rogado, Teresa Alonso-Gordoa, Georgia Dimopoulou, Sylvain Pradervand, Marco Tucci, Fanny Pommeret, and Marco Krengli
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Background As management and prevention strategies against COVID-19 evolve, it is still uncertain whether prior exposure to immune checkpoint inhibitors (ICIs) affects COVID-19 severity in patients with cancer.Methods In a joint analysis of ICI recipients from OnCovid (NCT04393974) and European Society for Medical Oncology (ESMO) CoCARE registries, we assessed severity and mortality from SARS-CoV-2 in vaccinated and unvaccinated patients with cancer and explored whether prior immune-related adverse events (irAEs) influenced outcome from COVID-19.Findings The study population consisted of 240 patients diagnosed with COVID-19 between January 2020 and February 2022 exposed to ICI within 3 months prior to COVID-19 diagnosis, with a 30-day case fatality rate (CFR30) of 23.6% (95% CI 17.8 to 30.7%). Overall, 42 (17.5%) were fully vaccinated prior to COVID-19 and experienced decreased CFR30 (4.8% vs 28.1%, p=0.0009), hospitalization rate (27.5% vs 63.2%, p
Published: 2022
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7. Metabolomic analyses of COVID-19 patients unravel stage-dependent and prognostic biomarkers

Author: François-Xavier Danlos, Claudia Grajeda-Iglesias, Sylvère Durand, Allan Sauvat, Mathilde Roumier, Delphine Cantin, Emeline Colomba, Julien Rohmer, Fanny Pommeret, Giulia Baciarello, Christophe Willekens, Marc Vasse, Frank Griscelli, Jean-Eudes Fahrner, Anne-Gaëlle Goubet, Agathe Dubuisson, Lisa Derosa, Nitharsshini Nirmalathasan, Delphine Bredel, Séverine Mouraud, Caroline Pradon, Annabelle Stoclin, Flore Rozenberg, Jérôme Duchemin, Georges Jourdi, Syrine Ellouze, Françoise Levavasseur, Laurence Albigès, Jean-Charles Soria, Fabrice Barlesi, Eric Solary, Fabrice André, Frédéric Pène, Félix Ackerman, Luc Mouthon, Laurence Zitvogel, Aurélien Marabelle, Jean-Marie Michot, Michaela Fontenay, and Guido Kroemer
Subjects: Cytology, QH573-671
Abstract: Abstract The circulating metabolome provides a snapshot of the physiological state of the organism responding to pathogenic challenges. Here we report alterations in the plasma metabolome reflecting the clinical presentation of COVID-19 patients with mild (ambulatory) diseases, moderate disease (radiologically confirmed pneumonitis, hospitalization and oxygen therapy), and critical disease (in intensive care). This analysis revealed major disease- and stage-associated shifts in the metabolome, meaning that at least 77 metabolites including amino acids, lipids, polyamines and sugars, as well as their derivatives, were altered in critical COVID-19 patient’s plasma as compared to mild COVID-19 patients. Among a uniformly moderate cohort of patients who received tocilizumab, only 10 metabolites were different among individuals with a favorable evolution as compared to those who required transfer into the intensive care unit. The elevation of one single metabolite, anthranilic acid, had a poor prognostic value, correlating with the maintenance of high interleukin-10 and -18 levels. Given that products of the kynurenine pathway including anthranilic acid have immunosuppressive properties, we speculate on the therapeutic utility to inhibit the rate-limiting enzymes of this pathway including indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase.
Published: 2021
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8. Dynamics of circulating calprotectin accurately predict the outcome of moderate COVID-19 patients

Author: Nicolas Chapuis, Nusaibah Ibrahimi, Thibaut Belmondo, Claire Goulvestre, Anne-Emmanuelle Berger, Alice-Andrée Mariaggi, Muriel Andrieu, Camille Chenevier-Gobeaux, Arnaud Bayle, Lydia Campos, Cherifa Cheurfa, Richard Chocron, Jean-Luc Diehl, Benoît Doumenc, Jérôme Duchemin, Manon Duprat, Fabien François, Nicolas Gendron, Tristant Mirault, Frédéric Pène, Aurélien Philippe, Fanny Pommeret, Olivier Sanchez, David M. Smadja, Tali-Anne Szwebel, Aymeric Silvin, Florent Ginhoux, Ludovic Lacroix, Gérôme Jules-Clément, Sarobidy Rapeteramana, Colette Mavier, Laura Steller, Barbara Perniconi, Fabrice André, Damien Drubay, Michaela Fontenay, Sophie Hüe, Stéphane Paul, and Eric Solary
Subjects: COVID-19, Calprotectin, S100A8/A9, Biomarker, Serial measurement, Dynamics, Medicine, Medicine (General), R5-920
Abstract: Summary: Background: Severe COVID-19 is associated with a high circulating level of calprotectin, the S100A8/S100A9 alarmin heterodimer. Baseline calprotectin amount measured in peripheral blood at diagnosis correlates with disease severity. The optimal use of this biomarker along COVID-19 course remains to be delineated. Methods: We focused on patients with a WHO-defined moderate COVID-19 requiring hospitalization in a medical ward. We collected plasma and serum from three independent cohorts (N = 626 patients) and measured calprotectin amount at admission. We performed longitudinal measures of calprotectin in 457 of these patients (1461 samples) and used a joint latent class mixture model in which classes were defined by age, body mass index and comorbidities to identify calprotectin trajectories predicting the risk of transfer into an intensive care unit or death. Findings: After adjustment for age, sex, body mass index and comorbidities, the predictive value of baseline calprotectin in patients with moderate COVID19 could be refined by serial monitoring of the biomarker. We discriminated three calprotectin trajectories associated with low, moderate, and high risk of poor outcome, and we designed an algorithm available as online software (https://calpla.gustaveroussy.fr:8443/) to monitor the probability of a poor outcome in individual patients with moderate COVID-19. Interpretation: These results emphasize the clinical interest of serial monitoring of calprotectin amount in the peripheral blood to anticipate the risk of poor outcomes in patients with moderate COVID-19 hospitalized in a standard care unit. Funding: The study received support (research grants) from ThermoFisher immunodiagnostics (France) and Gustave Roussy Foundation.
Published: 2022
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9. COVID-19 in breast cancer patients: a subanalysis of the OnCovid registry

Author: Laia Garrigós, Cristina Saura, Clara Martinez-Vila, Alberto Zambelli, Mark Bower, Barbara Pistilli, Matteo Lambertini, Diego Ottaviani, Nikolaos Diamantis, Ailsa Lumsden, Sonia Pernas, Daniele Generali, Elia Seguí, Gemma Viñas, Eudald Felip, Ana Sanchez, Gianpiero Rizzo, Armando Santoro, Alessio Cortellini, Ylenia Perone, John Chester, Maria Iglesias, Marta Betti, Bruno Vincenzi, Michela Libertini, Francesca Mazzoni, Federica Zoratto, Rossana Berardi, Annalisa Guida, Rachel Wuerstlein, Angela Loizidou, Rachel Sharkey, Juan Aguilar Company, Marta Matas, Chiara Saggia, Lorenzo Chiudinelli, Emeline Colomba-Blameble, Myria Galazi, Uma Mukherjee, Mieke Van Hemelrijck, Mar Marin, Carla Strina, Aleix Prat, Helena Pla, Eva Maria Ciruelos, Alexia Bertuzzi, Lucia del Mastro, Giampiero Porzio, Thomas Newsom-Davis, Isabel Ruiz, Maria Belen Delany, Marco Krengli, Vittoria Fotia, Alessandro Viansone, Neha Chopra, Margarita Romeo, Ramon Salazar, Ignacio Perez, Francesca d’Avanzo, Michela Franchi, Manuela Milani, Fanny Pommeret, Marco Tucci, Paolo Pedrazzoli, Nadia Harbeck, Daniela Ferrante, David J. Pinato, and Alessandra Gennari
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Background: Cancer patients are at higher risk of COVID-19 complications and mortality than the rest of the population. Breast cancer patients seem to have better prognosis when infected by SARS-CoV-2 than other cancer patients. Methods: We report a subanalysis of the OnCovid study providing more detailed information in the breast cancer population. Results: We included 495 breast cancer patients with a SARS-CoV-2 infection. Mean age was 62.6 years; 31.5% presented more than one comorbidity. The most frequent breast cancer subtype was luminal-like ( n = 245, 49.5%) and 177 (35.8%) had metastatic disease. A total of 332 (67.1%) patients were receiving active treatment, with radical intent in 232 (47.6%) of them. Hospitalization rate was 58.2% and all-cause mortality rate was 20.3%. One hundred twenty-nine (26.1%) patients developed one COVID-19 complication, being acute respiratory failure the most common ( n = 74, 15.0%). In the multivariable analysis, age older than 70 years, presence of COVID-19 complications, and metastatic disease were factors correlated with worse outcomes, while ongoing anticancer therapy at time of COVID-19 diagnosis appeared to be a protective factor. No particular oncological treatment was related to higher risk of complications. In the context of SARS-CoV-2 infection, 73 (18.3%) patients had some kind of modification on their oncologic treatment. At the first oncological reassessment (median time: 46.9 days ± 36.7), 255 (51.6%) patients reported to be fully recovered from the infection. There were 39 patients (7.9%) with long-term SARS-CoV-2-related complications. Conclusion: In the context of COVID-19, our data confirm that breast cancer patients appear to have lower complications and mortality rate than expected in other cancer populations. Most breast cancer patients can be safely treated for their neoplasm during SARS-CoV-2 pandemic. Oncological treatment has no impact on the risk of SARS-CoV-2 complications, and, especially in the curative setting, the treatment should be modified as little as possible.
Published: 2021
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10. Validation of the geriatric vulnerability score in older patients with ovarian cancer: an analysis from the GCIG-ENGOT-GINECO EWOC-1 study

Author: Claire Falandry, Fanny Pommeret, Laurence Gladieff, Fabien Tinquaut, Domenica Lorusso, Marie-Ange Mouret-Reynier, Véronique D'Hondt, Delphine Mollon-Grange, Anne Floquet, Sophie Abadie-Lacourtoisie, Pierre-Emmanuel Brachet, Laetitia Stefani, Frédérique Rousseau, Jean-Sébastien Frenel, Francesco Del Piano, Marja Komulainen, Thomas Warkus, Olivier Trédan, Eric Pujade-Lauraine, and Gilles Freyer
Subjects: Ovarian Neoplasms, Psychiatry and Mental health, Health (social science), Paclitaxel, Antineoplastic Combined Chemotherapy Protocols, Humans, Female, Carcinoma, Ovarian Epithelial, Geriatrics and Gerontology, Family Practice, Aged, Carboplatin
Abstract: Older patients with ovarian cancer represent a heterogeneous population. The French National Group of Investigators for the Study of Ovarian and Breast Cancer developed the geriatric vulnerability score (GVS) to identify geriatric parameters predictive of poor outcomes. A prospective validation of the GVS was needed.The EWOC-1 study (NCT02001272) was an international, open-label, phase 2, three-arm trial designed according to a two-step process. Patients aged 70 years or older with newly diagnosed stage III or IV ovarian cancer were identified and the GVS determined. Those with a GVS of 3 or greater were randomly assigned to the EWOC-1 trial, stratified by country and surgical outcome, to receive three different carboplatin with or without paclitaxel regimens; those not included in the EWOC-1 trial were followed up in the EWOC-1 registry. External validation of the GVS was a secondary endpoint of the trial. Three validation cohorts were identified: the total population (validation cohort 1 [V1], n=447), the registry-only population (validation cohort 2 [V2], n=327), and the carboplatin-paclitaxel-treated population (validation cohort 3 [V3], n=320).From Dec 11, 2013, to Nov 16, 2018, 447 patients were included in 48 academic centres in six countries; 120 in the EWOC-1 trial and 327 in the EWOC-1 registry. Median follow-up was 19·7 (95% CI 8·5-29·7) months for the total cohort; missing values were low (2%). According to the maximum likelihood analysis, the hazard ratio (HR) of death in V1 was 1·8 (95% CI 1·1-3·1, p=0·029) for those with a GVS of 1; 2·4 (1·4-4·0, p=0·0009) with a GVS of 2; 4·1 (2·5-7·0, p0·0001) for a GVS of 3; 5·5 (3·3-9·3, p0·0001) for a GVS of 4; and 9·1 (4·7-17·5, p0·0001) for a GVS of 5 compared with a score of 0. Whatever the validation cohort, GVS of 3 or more significantly segregated two groups with different overall survival: V1 (median 13·2 [95% CI: 10·8-18·7] vs 40·8 [32·0-45·6] months; HR 2·8 [95% CI 2·2-3·7]; p0·0001); V2 (11·9 [95% CI 8·8-18·1] vs 40·8 [32·0-45·6] months, HR 3·5 [2·5-4·9]; p0·0001); and V3 (18·1 [95% CI 15·8-31·8] vs 43·0 [40·6-49·7] months, HR 2·6 [1·9 to 3·7]; p0·0001).The GVS has high prognostic performance for overall survival in patients with advanced ovarian cancer, independently of geographic and historic effect (V1), as well as treatment patterns (V3), validated in an international population. Even though the GVS is time consuming it will allow the stratification of populations for clinical research and might permit the orientation of the geriatric intervention to specific domains.French National Cancer Institute.For the French translation of the abstract see Supplementary Materials section.
Published: 2022
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11. Data from The Polarity and Specificity of Antiviral T Lymphocyte Responses Determine Susceptibility to SARS-CoV-2 Infection in Patients with Cancer and Healthy Individuals

Author: Laurence Zitvogel, Lisa Derosa, Markus Maeurer, Bernard La Scola, Guido Kroemer, Odile Launay, Emma Guttman-Yassky, Florence Fenollar, Sophie Caillat-Zucman, Mathieu F. Chevalier, Juliette Villemonteix, Fabrice André, Miriam Merad, Jean-Charles Soria, Jean-Yves Blay, Frank Griscelli, Aurélien Marabelle, Florian Scotté, Mansouria Merad, Jean-Philippe Spano, Bertrand Gachot, Eric Deutsch, Nathalie Droin, Marc Deloger, Pernelle Lavaud, Emeline Colomba, Fanny Pommeret, Emmanuelle Gallois, Caroline Pradon, Yeriel Estrada, Benjamin Ungar, Alexandre Trubert, Fabrice Barlesi, Guy Gorochov, Makoto Miyara, Abdelhakim Ahmed-Belkacem, Lydia Meziani, Nadine Benhamouda, Eric Tartour, Pierre Ly, Caroline Flament, Eugenie Pizzato, Safae Terrisse, François-Xavier Danlos, Marianne Gazzano, Benoît Kloeckner, Alice Bernard-Tessier, Ariane Laparra, Joana R. Lérias, Luigi Cerbone, Marion Picard, Camille Bigenwald, Roxanne Birebent, Gladys Ferrere, Arthur Geraud, Agathe Dubuisson, Cléa Melenotte, Cassandra Thelemaque, Eric de Sousa, Carolina Alves Costa Silva, Damien Drubay, Marine Mazzenga, Agathe Carrier, Yacine Haddad, Anne-Gaëlle Goubet, Imran Lahmar, and Jean-Eudes Fahrner
Abstract: Vaccination against coronavirus disease 2019 (COVID-19) relies on the in-depth understanding of protective immune responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We characterized the polarity and specificity of memory T cells directed against SARS-CoV-2 viral lysates and peptides to determine correlates with spontaneous, virus-elicited, or vaccine-induced protection against COVID-19 in disease-free and cancer-bearing individuals. A disbalance between type 1 and 2 cytokine release was associated with high susceptibility to COVID-19. Individuals susceptible to infection exhibited a specific deficit in the T helper 1/T cytotoxic 1 (Th1/Tc1) peptide repertoire affecting the receptor binding domain of the spike protein (S1-RBD), a hotspot of viral mutations. Current vaccines triggered Th1/Tc1 responses in only a fraction of all subject categories, more effectively against the original sequence of S1-RBD than that from viral variants. We speculate that the next generation of vaccines should elicit Th1/Tc1 T-cell responses against the S1-RBD domain of emerging viral variants.Significance:This study prospectively analyzed virus-specific T-cell correlates of protection against COVID-19 in healthy and cancer-bearing individuals. A disbalance between Th1/Th2 recall responses conferred susceptibility to COVID-19 in both populations, coinciding with selective defects in Th1 recognition of the receptor binding domain of spike.See related commentary by McGary and Vardhana, p. 892.This article is highlighted in the In This Issue feature, p. 873
Published: 2023
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12. Supplementary Figure from The Polarity and Specificity of Antiviral T Lymphocyte Responses Determine Susceptibility to SARS-CoV-2 Infection in Patients with Cancer and Healthy Individuals

Author: Laurence Zitvogel, Lisa Derosa, Markus Maeurer, Bernard La Scola, Guido Kroemer, Odile Launay, Emma Guttman-Yassky, Florence Fenollar, Sophie Caillat-Zucman, Mathieu F. Chevalier, Juliette Villemonteix, Fabrice André, Miriam Merad, Jean-Charles Soria, Jean-Yves Blay, Frank Griscelli, Aurélien Marabelle, Florian Scotté, Mansouria Merad, Jean-Philippe Spano, Bertrand Gachot, Eric Deutsch, Nathalie Droin, Marc Deloger, Pernelle Lavaud, Emeline Colomba, Fanny Pommeret, Emmanuelle Gallois, Caroline Pradon, Yeriel Estrada, Benjamin Ungar, Alexandre Trubert, Fabrice Barlesi, Guy Gorochov, Makoto Miyara, Abdelhakim Ahmed-Belkacem, Lydia Meziani, Nadine Benhamouda, Eric Tartour, Pierre Ly, Caroline Flament, Eugenie Pizzato, Safae Terrisse, François-Xavier Danlos, Marianne Gazzano, Benoît Kloeckner, Alice Bernard-Tessier, Ariane Laparra, Joana R. Lérias, Luigi Cerbone, Marion Picard, Camille Bigenwald, Roxanne Birebent, Gladys Ferrere, Arthur Geraud, Agathe Dubuisson, Cléa Melenotte, Cassandra Thelemaque, Eric de Sousa, Carolina Alves Costa Silva, Damien Drubay, Marine Mazzenga, Agathe Carrier, Yacine Haddad, Anne-Gaëlle Goubet, Imran Lahmar, and Jean-Eudes Fahrner
Abstract: Supplementary Figure from The Polarity and Specificity of Antiviral T Lymphocyte Responses Determine Susceptibility to SARS-CoV-2 Infection in Patients with Cancer and Healthy Individuals
Published: 2023
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13. Supplementary Data from The Polarity and Specificity of Antiviral T Lymphocyte Responses Determine Susceptibility to SARS-CoV-2 Infection in Patients with Cancer and Healthy Individuals

Author: Laurence Zitvogel, Lisa Derosa, Markus Maeurer, Bernard La Scola, Guido Kroemer, Odile Launay, Emma Guttman-Yassky, Florence Fenollar, Sophie Caillat-Zucman, Mathieu F. Chevalier, Juliette Villemonteix, Fabrice André, Miriam Merad, Jean-Charles Soria, Jean-Yves Blay, Frank Griscelli, Aurélien Marabelle, Florian Scotté, Mansouria Merad, Jean-Philippe Spano, Bertrand Gachot, Eric Deutsch, Nathalie Droin, Marc Deloger, Pernelle Lavaud, Emeline Colomba, Fanny Pommeret, Emmanuelle Gallois, Caroline Pradon, Yeriel Estrada, Benjamin Ungar, Alexandre Trubert, Fabrice Barlesi, Guy Gorochov, Makoto Miyara, Abdelhakim Ahmed-Belkacem, Lydia Meziani, Nadine Benhamouda, Eric Tartour, Pierre Ly, Caroline Flament, Eugenie Pizzato, Safae Terrisse, François-Xavier Danlos, Marianne Gazzano, Benoît Kloeckner, Alice Bernard-Tessier, Ariane Laparra, Joana R. Lérias, Luigi Cerbone, Marion Picard, Camille Bigenwald, Roxanne Birebent, Gladys Ferrere, Arthur Geraud, Agathe Dubuisson, Cléa Melenotte, Cassandra Thelemaque, Eric de Sousa, Carolina Alves Costa Silva, Damien Drubay, Marine Mazzenga, Agathe Carrier, Yacine Haddad, Anne-Gaëlle Goubet, Imran Lahmar, and Jean-Eudes Fahrner
Abstract: Supplementary Data from The Polarity and Specificity of Antiviral T Lymphocyte Responses Determine Susceptibility to SARS-CoV-2 Infection in Patients with Cancer and Healthy Individuals
Published: 2023
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14. Sarilumab in adults hospitalised with moderate-to-severe COVID-19 pneumonia (CORIMUNO-SARI-1): An open-label randomised controlled trial

Author: Anatole Harrois, Florence Patin, Anaïs Razurel, Laure Allanic, Grégoire Martin de Frémont, Vincent Jachiet, Gonçalo Boleto, Eric D'Ortenzio, Xavier Mariette, Philippe Dieudé, Etienne Canouï, Z Julia, Nathalie Dournon, Jean-Sébastien Hulot, David Lebeaux, Eric Mariotte, Dorothee Vallois, Laurence Berard, Nicolas Gambier, Christiane Verny, Mathilde Le Marchand, Mitja Jevnikar, Jean-Jacques Mourad, Marjolaine Morgand, Bertrand Guidet, Alexandre Moores, Prissile Bakouboula, Frédéric Pène, Pascal Richette, Martine Meunier, Juliette Camuset, Stéphane Jauréguiberry, Lynda Chalal, Mamadou Salif Cisse, Marie-Hélène Legros, Yann Nguyen, Damien Roux, Robin Deleris, Maxence Decavele, Patrice Cacoub, Isabelle Dusanter, Patricia Senet, Nassim Mahtal, Raphael Borie, Philippe Benoit, Blandine Denis, Luca Semerano, Sebastien Abad, Marie Dubert, Marie Lachatre, Marine Livrozet, Nathan Ebstein, Lakhdar Mameri, Adrien Michon, Olivier Sanchez, Aurélien Guffroy, Pierre Dupland, Jérôme Pacanowski, Yasmina Ferfar, Tassadit Hadjam, Anne-Marie Roques, Celine Comparon, Solaya Chalal, A Soria, Isabelle Lehir, Anne Gysembergh-Houal, Stéphanie Alary, Valérie Dejean, Elena Kiouris, Estelle Henry, Sophie Diemunsch, Jonathan London, Fanny Charbonnier, Alexandre Demoule, Louise Bondeelle, Samira Saleh-Mghir, Lise Bernard, Brigitte Sabatier, Anne Jacolot, Aurelie Sautereau, Pierre Faye, Benjamin Fournier, Noémie Abisror, Awa Ndiaye, Ruben Benainous, Damien Sène, Emmanuelle Sacco, Isabelle Debrix, Gabriel Nisand, Régis Peffault de Latour, Anne Sophie Korganow, Kévin Cardet, Perrine Guillaume-Jugnot, Soumeya Hammal, B. Duchemann, Elena Fois, Jean-Benoit Arlet, Christine Broissand, Yaël Amara, Matheus Vieira, Sophie Caillat-Zucman, Madona Sakkal, Juliette Djadi-Prat, Jean-Louis Teboul, Hélène François, Stéphane Renaud, Sylviane Ravato, Alaki Thiemele, Gabrielle Archer, Alain Fourreau, David Boutboul, Arsène Mekinian, Antoine Gros, Morgane Faure, Anne Pattyn, Camille Petit-Hoang, Jessica Krause le Garrec, Antony Canellas, Jean-Michel Molina, Zakaria Ait Hamou, Eric Oksenhendler, Ilias Koumis, Marie-Aude Penet, Catherine Boussard, Vincent Fallet, Guillaume Geri, Loic Kassegne, Bernard Cholley, Lucie Biard, Elodie Perrodeau, Tomas Urbina, David Schmitz, johann Cailhol, Elise Morawiec, Audrey Phibel, Sophie Renet, Emmanuel Weiss, Faouzi Saliba, Kristina Beziriganyan, Abdellatif Tazi, Isabelle Peigney, Bertrand Dunogue, Rémy Gauzit, Damien Bergerot, Bob Heger, Ines Ben-Mabrouk, Jade Ghosn, Benjamin Planquette, Alexis Régent, François Weill, Yasmina Mekid, Rosa Da Silva, Victor Lancon, Marc Michel, Nadia Anguel, Anne Claire Desbois, François Danion, Brigitte Ranque, Mohamed Belloul, Nadège Lemarié, Amélie Cransac, Marine Nadal, Lalia Djaghout, Anne Tréhan, Samy Figueiredo, Hakim Meddah, Aurélie Clan Hew Wai, Julie Delemazure, Soraya Fellahi, Jacques-Eric Gottenberg, Matthieu Uzzan, Jean-Charles Duclos-Vallée, Tabassome Simon, Vanessa Rathouin, Yves Hansmann, Hélène Gros, Syllia Belazouz, Nathalie Marin, Camille Rolland-Debord, Edouard Lefèvre, Sophie-Rym Hamada, Tristan Martin, Annabelle Stoclin, Frédéric Duée, Helene Chambrin-Lauvray, Ramdane Meftali, Miguel Alejandro Vasquez-Ibarra, Isabelle Madeleine, Simon Valayer, Anne Adda, Marie-Thérèse Tremorin, Nicolas Meyer, Vixra Keo, Lara Zafrani, Caroline Semaille, Maxime Dougados, Olivier Olivier, Emeline Colomba, Florence Morin, Claire Rouzaud, Paul Michel Mertes, Claire Montlahuc, Anne Blanchard, Valérie Pourchet-Martinez, Constance Delaugerre, Nicolas Carlier, Jacques Cadranel, Nicolas Noel, Kahina Cheref, Bao Phung, Moez Jallouli, Ulrich Clarac, Marthe Rigal, Mireille Adda, Lionel Galicier, Fanny Domont, Lee S. Nguyen, Férial Berbour, Fanny Pommeret, Celine Dupré, Gaël Leprun, Jean-Luc Diehl, Laetitia Languille, Philippe Blanche, Abolfazl Mohebbi, Mathilde Noaillon, Olivier Collange, Paul Jaubert, Anne Daguenel-Nguyen, Sandrine Briois, Anne-Lise Pouliquen, Coralie Bloch Queyrat, Clément Jourdaine, Cédric Pierron, Geoffrey Rossi, Chloe McAvoy, Claire Courtin, Mathias Cornic, C Rioux, Christine Lemagner, Martin Dres, Emmanuelle Guillot, Marc Garnier, Safaa Nemlaghi, Guillaume Grailles, Yazdan Yazdanpanah, Veronique Joly, Thiziri Sadaoui, Marion Bouhris, Vincent Castelain, Muriel Fartoukh, Sébastien Cavelot, Sophie Ohlmann-Caillard, Valentina Isernia, Bruno Crestani, Thinhinane Bariz, Benjamin Chaigne, Emmanuel Andrès, Frédéric Blanc, Alain Wynckel, Louise-Laure Mariani, Yasmine Messaoudi, Naima Sguiouar, Amina Kebir, Asmaa Mamoune, Caroline Gaudefroy, Victoire De Lastours, Pierre Diemunsch, Etienne Lengliné, Claire Tantet, Julien Mayaux, Benjamin G. Chousterman, Arthur Pavot, Anne Rachline, Gwenaël Lorillon, Hassan Joumaa, Nicolas Lefebvre, Elodie Baudry, Nicolas Bonnet, Fanny Defrancq, Véronique Vigna, Yves Cohen, Amira Benattia, Martin Siguier, Sophie Georgin-Lavialle, Emmanuelle Bugnet, Lamiae Grimaldi, Olivia Daconceicao, Olivier Hermine, Mathieu Vautier, Florence Tubach, Marion Licois, Anaïs Codorniu, Fanny Alby-Laurent, Jérémie Zerbit, Aude Jacob, Benedicte Giroux-Leprieur, Carine Karachi, Laurent Cylly, Edouard Flamarion, Gladys Aratus, Charléne Jouve, Robin Dhote, Claire Davoine, Valentin Greigert, Gaelle Leroux, Cécile Kedzia, Guillaume Lefèvre, Catherine Metzger, Olivier Benveniste, Clairelyne Dupin, Marie-Alexandra Alyanakian, Mathieu Oberlin, Julien Poissy, Linda Gimeno, Adrien Contejean, Segolene Toquet, Jeanne CHAUFFiER, Mathieu Jozwiak, Laurent Savale, Virginie Zarrouk, Cécile Yelnik, Mandy Nizard, Mourad Djadel, F-Xavier Lescure, Agnes Maurer, Geoffroy Liégeon, Arthur Neuschwander, Hélène Lafoeste, Gaëtan Deslée, Frédéric De Blay, Claire Pernin, Cloé Comarmond, Anne Hutt, Ridha Belilita, Laurence Lecomte, Sophie-Caroline Sacleux, Nathalie Rozensztajn, Jean-Jacques Tudesq, Benjamin Terrier, Solène Fabre, Lelia Escaut, Eva Chatron, Emmanuelle Blin, Pauline Jouany, Sara Sambin, Chistophe Willekens, Nabil Raked, Jean-Simon Rech, Serge Bureau, Boris Bienvenu, Elisabeth Coupez, Tali-Anne Szwebel, Lydia Suarez, Chaouki Bouras, Kamyl Baghli, Emilia Stan, Valérie Camara-Clayette, Fanette Denies, Nathalie Menage, Paul Legendre, Axelle Fuentes, Oriane Puéchal, Charlotte Kaeuffer, Guillaume Becker, Clara Campos-Vega, Armand Mekontso-Dessaps, Pernelle Vauboin, Yurdagul Uzunhan, F Louni, Marie hélène Pari, Myriam Virlouvet, Nicolas Belaube, Hugues Cordel, Nathalie Chavarot, Olivier Sitbon, Jean-Daniel Lelievre, Matthieu Mahévas, Julie Smati, Olivier Clovet, Marc Bardou, Ada Clarke, Gilles Garcia, Anouk Walter-Petrich, Hala Semri, Vasco Honsel, Giovanna Melica, Pierre Mora, Olivier Fain, A Gervais, Marc Humbert, Yves Allenbach, Céline Verstuyft Verstuyft, Blandine Lehmann, Pascal Martel, Aida Zahrate-Ghoul, Karine Martin, Alexandre Bourgoin, Baptiste Duceau, Philippe Ravaud, Celine Wilpotte, Sylvie Le Gac, Michaël Darmont, Aurélie Durel Maurisse, Younes Keroumi, Aude Rigolet, Julie Chas, Pierre-Louis Tharaux, Caroline Morbieu, Valérie Paquet, Eric Vicaut, Pascaline Choinier, Samir Hamiria, Elsa Feredj, Frédéric Schlemmer, Gilles Pialoux, Zeina Louis, Marion Parisey, David Montani, Jean-Pierre Riveline, Jean-Marie Michot, Pascal Lim, Eliane Bertrand, Gaelle Clavere, Julie Jambon, Stéphane Brin, Saskia Flamand, Jeanne Meunier, Geoffroy Volle, Martin De Sarcus, Marie Vayssettes, Thomas Papo, Caroline Hauw-Berlemont, Gabriel Baron, Jeremy Arzoine, Loren Soyez-Herkert, Maria Pereira, Antoine Parrot, Johanna Oziel, Carole Burger, Eric Noll, Paul Vermes, Jeanne Goupil de Bouille, Xavier Monnet, Paul Crespin, Sarah Dalibey, Thierno Dieye, Renaud Felten, Jean-Philippe Bastard, Younes El Amine, Timothee Bironne, Damien Vanhoye, Amine Ghembaza, Laure Berton, Yvon Ruch, Thomas Volpe, Thomas Gorget, Jaouad Benhida, Julien Saussereau, Elodie Issorat, Virginie Elisee, Adrien Mirouse, Cecile Larcheveque, Laurène Deconinck, A. Dossier, Félix Ackermann, Greggory Ducrocq, Anne Bergeron, Laurence Annonay, Camille Knosp, Laurence Drouard, Adrien Joseph, Hilario Nunes, Hanane Fodil, Sabrine Ouamri, Belkacem Asselate, Julie Fillon, Dominique Dautel, Isabelle Brindele, Robin Charreteur, S Lariven, Elie Azoulay, Sami Kolta, Cédric Sublon, Florence Bellenfant, Melissa Clément, Lola-Jade Palmieri, Bruno Mourvillier, Ewa Kozaliewicz, Vincent Provitolo, Marie Lecronier, Julien Chabert, Matthieu Resche-Rigon, Stéphan Pavy, Naura Gamany, Dorothée Chopin, Aïcha Bah, Moustafa Benafla, Corinne Guerin, Pierre Tissieres, Nathalie Costedoat-Chalumeau, Nessima Yelles, Emmanuel Chatelus, Jean-Christophe Corvol, Luc Mouthon, Marie Gilbert, Matthieu Lemoine, Lucie Aunay, Candice Estellat, Laure Choupeaux, Dhiaa Meriem Hai, Bernard Goichot, Céline Louapre, Roza Rahli, Nathalie De Castro, Christian Richard, Malikhone Chansombat, Kamil Chitour, Joseph Emmerich, Elodie Drouet, Julien Pottecher, Eric Demonsant, Alexandra Beurton, Raphaël Porcher, Lauren Demerville, Amélie Servettaz, Annabelle Pourbaix, Philippe Manivet, Pierre-Grégoire Guinot, Nicolas Champtiaux, Caroline Pradon, Annick Tibi, Julien Le Marec, Nawal Derridj, Mohamad Zaidan, Eric Marquis, Mickael Henriques, Bruno Mégarbane, Aline Frazier, Ramon Junquera, Diane Le Pluart, Coralie Gernez, Yacine Boudali, Dimitri Fremont, Pierrick Le Borgne, Corinne Pernot, Mélanie Dehais, Claire Madelaine, Dominique Roulot, Georgina Maalouf, Constance Guillaud, Corine Nyanou, Karine Celli Lebras, Sophie Granville, Sabrina Brahmi, Catherine Le Bourlout, Hassan Tarhini, Asmaa Mabrouki, Hakim Tayebi, Sophie Ismael, Jonathan Marey, Sophie Bayer, Gabriel Steg, Antoine Fayol, Catherine Fauvaux, Delphine Feyeux, Côme Bureau, Alexandre Morel, Agathe Bounhiol, Alexandre Buffet, Souad Benarab, Luc Haudebourg, Pierre Le Guen, Damien Vimpere, Xavier Jaïs, Clotilde Le Tiec Le Tiec, Sophie Bulifon, Pélagie Thibaut, Alison Klasen, Claire Pacheco, Anne Godier, Marie Antignac, Domitille Molinari, Philippe Durand, Olivier Lambotte, Paul Henri Grisot, Anne Lise Jegu, Vincent Poindron, Ruxandra Burlacu, Denis Jesuthasan, Sarah Benghanem, Solen Kernéis, Antoine Bachelard, Jacques Duranteau, Karine Lacombe, Olivia Lenoir, Mathilde Vallet, Sara Virolle, Léa Resmini, Liem Binh Luong Nguyen, Marie Matignon, Céline Leplay, and Claire Aguilar
Subjects: medicine.medical_specialty, business.industry, Immunology, Hazard ratio, Absolute risk reduction, Articles, medicine.disease, law.invention, Clinical trial, Pneumonia, Sarilumab, Rheumatology, Randomized controlled trial, law, Internal medicine, Cohort, medicine, Immunology and Allergy, Adverse effect, business
Abstract: Summary Background Patients with COVID-19 pneumonia can have increased inflammation and elevated cytokines, including interleukin (IL)-6, which might be deleterious. Thus, sarilumab, a high-affinity anti-IL-6 receptor antibody, might improve the outcome of patients with moderate-to-severe COVID-19 pneumonia. Methods We did a multicentric, open-label, Bayesian randomised, adaptive, phase 2/3 clinical trial, nested within the CORIMUNO-19 cohort, to test a superiority hypothesis. Patients 18 years or older hospitalised with COVID-19 in six French centres, requiring at least 3L/min of oxygen but without ventilation assistance and a WHO Clinical Progression Scale [CPS] score of 5 were enrolled. Patients were randomly assigned (1:1) via a web-based system, according to a randomisation list stratified on centre and with blocks randomly selected among 2 and 4, to receive usual care plus 400 mg of sarilumab intravenously on day 1 and on day 3 if clinically indicated (sarilumab group) or usual care alone (usual care group). Primary outcomes were the proportion of patients with WHO-CPS scores greater than 5 on the 10-point scale on day 4 and survival without invasive or non-invasive ventilation at day 14. This completed trial is closed to new participants and is registered with ClinicalTrials.gov , NCT04324073 . Findings 165 patients were recruited from March 27 to April 6, 2020, and 148 patients were randomised (68 patients to the sarilumab group and 80 to the usual care group) and followed up for 90 days. Median age was 61·7 years [IQR 53·0–71·1] in the sarilumab group and 62·8 years [56·0–71·7] in the usual care group. In the sarilumab group 49 (72%) of 68 were men and in the usual care group 59 (78%) of 76 were men. Four patients in the usual care group withdrew consent and were not analysed. 18 (26%) of 68 patients in the sarilumab group had a WHO-CPS score greater than 5 at day 4 versus 20 (26%) of 76 in the usual care group (median posterior absolute risk difference 0·2%; 90% credible interval [CrI] −11·7 to 12·2), with a posterior probability of absolute risk difference greater than 0 of 48·9%. At day 14, 25 (37%) patients in the sarilumab and 26 (34%) patients in the usual care group needed ventilation or died, (median posterior hazard ratio [HR] 1·10; 90% CrI 0·69–1·74) with a posterior probability HR greater than 1 of 37·4%. Serious adverse events occurred in 27 (40%) patients in the sarilumab group and 28 (37%) patients in the usual care group (p=0·73). Interpretation Sarilumab treatment did not improve early outcomes in patients with moderate-to-severe COVID-19 pneumonia. Further studies are warranted to evaluate the effect of sarilumab on long-term survival. Funding Assistance publique—Hopitaux de Paris
Published: 2022
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15. SARS-CoV-2 omicron (B.1.1.529)-related COVID-19 sequelae in vaccinated and unvaccinated patients with cancer: results from the OnCovid registry

Author: Alessio Cortellini, Josep Tabernero, Uma Mukherjee, Ramon Salazar, Anna Sureda, Clara Maluquer, Daniela Ferrante, Mark Bower, Rachel Sharkey, Oriol Mirallas, Andrea Plaja, Marc Cucurull, Ricard Mesia, Alessia Dalla Pria, Thomas Newsom-Davis, Mieke Van Hemelrijck, Ailsa Sita-Lumsden, Eleanor Apthorp, Bruno Vincenzi, Giuseppina Rita Di Fazio, Giuseppe Tonini, Francesco Pantano, Alexia Bertuzzi, Sabrina Rossi, Joan Brunet, Matteo Lambertini, Paolo Pedrazzoli, Federica Biello, Francesca D'Avanzo, Alvin J X Lee, Marianne Shawe-Taylor, Lucy Rogers, Cian Murphy, Lee Cooper, Ramis Andaleeb, Saira Khalique, Samira Bawany, Sarah Ahmed, M Carmen Carmona-García, Roser Fort-Culillas, Raquel Liñan, Federica Zoratto, Gianpiero Rizzo, Marta Perachino, Kris Doonga, Gianluca Gaidano, Riccardo Bruna, Andrea Patriarca, Clara Martinez-Vila, Ignacio Pérez Criado, Raffaele Giusti, Francesca Mazzoni, Lorenzo Antonuzzo, Armando Santoro, Alessandro Parisi, Paola Queirolo, Avinash Aujayeb, Lorenza Rimassa, Nikolaos Diamantis, Rossella Bertulli, Claudia A M Fulgenzi, Antonio D'Alessio, Isabel Ruiz-Camps, Nadia Saoudi-Gonzalez, David Garcia Illescas, Irene Medina, Laura Fox, Alessandra Gennari, Juan Aguilar-Company, David J Pinato, Joanne S Evans, Judith Swallow, Georgina Hanbury, Chris Chung, Meera Patel, Gino Dettorre, Katherine Belessiotis, Dolly Saorise, Eleanor Jones, Charlotte Moss, Beth Russell, Sarah Townsend, Amanda Jackson, Angela Loizidou, Martine Piccart, Fanny Pommeret, Emeline Colomba-Blameble, Aleix Prat, Claudia A Cruz, Roxana Reyes, Elia Segui, Javier Marco-Hernández, Margarita Viladot, Nadia Harbeck, Rachel Wuerstlein, Franziska Henze, Sven Mahner, Eudald Felip, Lorenza Scotti, Andrea Marrari, Federica Grosso, Vittorio Fusco, Sara Delfanti, Maura Rossi, Alberto Zambelli, Carlo Tondini, Lorenzo Chiudinelli, Michela Franchi, Michela Libertini, Salvatore Provenzano, Daniele Generali, Salvatore Grisanti, Alice Baggi, Valeria Tovazzi, Corrado Ficorella, Giampiero Porzio, Maristella Saponara, Marco Filetti, Marco Tucci, Rossana Berardi, Luca Cantini, Francesco Paoloni, Annalisa Guida, Sergio Bracarda, Maria Iglesias, Ana Sanchez de Torre, and Marco Tagliamento
Subjects: Malalts de càncer, Oncology, SARS-CoV-2, Vaccination, COVID-19, Cancer patients, Vacunació
Abstract: Background COVID-19 sequelae can affect about 15% of patients with cancer who survive the acute phase of SARS-CoV-2 infection and can substantially impair their survival and continuity of oncological care. We aimed to investigate whether previous immunisation affects long-term sequelae in the context of evolving variants of concern of SARS-CoV-2. Methods OnCovid is an active registry that includes patients aged 18 years or older from 37 institutions across Belgium, France, Germany, Italy, Spain, and the UK with a laboratory-confirmed diagnosis of COVID-19 and a history of solid or haematological malignancy, either active or in remission, followed up from COVID-19 diagnosis until death. We evaluated the prevalence of COVID-19 sequelae in patients who survived COVID-19 and underwent a formal clinical reassessment, categorising infection according to the date of diagnosis as the omicron (B.1.1.529) phase from Dec 15, 2021, to Jan 31, 2022; the alpha (B.1.1.7)-delta (B.1.617.2) phase from Dec 1, 2020, to Dec 14, 2021; and the pre-vaccination phase from Feb 27 to Nov 30, 2020. The prevalence of overall COVID-19 sequelae was compared according to SARS-CoV-2 immunisation status and in relation to post-COVID-19 survival and resumption of systemic anticancer therapy. This study is registered with ClinicalTrials.gov, NCT04393974. Findings At the follow-up update on June 20, 2022, 1909 eligible patients, evaluated after a median of 39 days (IQR 24-68) from COVID-19 diagnosis, were included (964 [ 50 center dot 7%] of 1902 patients with sex data were female and 938 [49 center dot 3%] were male). Overall, 317 (16 center dot 6%; 95% CI 14 center dot 8-18 center dot 5) of 1909 patients had at least one sequela from COVID-19 at the first oncological reassessment. The prevalence of COVID-19 sequelae was highest in the prevaccination phase (191 [19 center dot 1%; 95% CI 16 center dot 4-22 center dot 0] of 1000 patients). The prevalence was similar in the alpha-delta phase (110 [16 center dot 8%; 13 center dot 8- 20 center dot 3] of 653 patients, p=0 center dot 24), but significantly lower in the omicron phase (16 [6 center dot 2%; 3 center dot 5-10 center dot 2] of 256 patients, p
Published: 2023

16. Severe COVID-19 in patients with hematological cancers presenting with viremia

Author: P.H. Cournède, Fanny Pommeret, Stéphanie Foulon, J-C. Soria, Bertrand Gachot, Arnaud Bayle, Thomas Hueso, Vincent Ribrag, Christophe Willekens, S. Francis, Fabrice Barlesi, Emeline Colomba, Laurence Albiges, J-M. Michot, N. Ibrahimi, M. Merad, and Frank Griscelli
Subjects: 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), SARS-CoV-2, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), MEDLINE, COVID-19, Viremia, Hematology, medicine.disease, Virology, Hospitalization, Oncology, Hematologic Neoplasms, medicine, Humans, In patient, business, Letter to the Editor
Published: 2021
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17. Immune checkpoint inhibitor therapy and outcomes from SARS-CoV-2 infection in patients with cancer: a joint analysis of OnCovid and ESMO-CoCARE registries

Author: Alessio Cortellini, Gino M Dettorre, Urania Dafni, Juan Aguilar-Company, Luis Castelo-Branco, Matteo Lambertini, Spyridon Gennatas, Vasileios Angelis, Ailsa Sita-Lumsden, Jacobo Rogado, Paolo Pedrazzoli, David Viñal, Aleix Prat, Maura Rossi, Rossana Berardi, Teresa Alonso-Gordoa, Salvatore Grisanti, Georgia Dimopoulou, Paola Queirolo, Sylvain Pradervand, Alexia Bertuzzi, Mark Bower, Dirk Arnold, Ramon Salazar, Marco Tucci, Kevin J Harrington, Francesca Mazzoni, Uma Mukherjee, Zoi Tsourti, Olivier Michielin, Fanny Pommeret, Joan Brunet, Bruno Vincenzi, Giuseppe Tonini, Andrea Patriarca, Federica Biello, Marco Krengli, Josep Tabernero, George Pentheroudakis, Alessandra Gennari, Solange Peters, Emanuela Romano, David J Pinato, Institut Català de la Salut, [Cortellini A] Department of Surgery & Cancer, Hammersmith Hospital Campus, Imperial College London, London, UK. Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy. [Dettorre GM] Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA. [Dafni U] Laboratory of Biostatistics, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece. [Aguilar-Company J] Servei d’Oncologia Mèdica, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei de Malalties Infeccioses, Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Castelo-Branco L] Scientific and Medical Division, ESMO (European Society for Medical Oncology), Lugano, Switzerland. NOVA National School of Publich Health, NOVA University, Lisbon, Portugal. [Lambertini M] Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genoa, Genova, Italy. Medical Oncology Department, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy, Vall d'Hebron Barcelona Hospital Campus, and Wellcome Trust
Subjects: Cytotoxicity, Immunologic, Cancer Research, Immunology, Immunoteràpia, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Immunotheraphy, Vacunes, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Medical Oncology, COVID-19 (Malaltia), Cell-mediated cytotoxicity, neoplasias [ENFERMEDADES], Immunitat cel·lular, Immunogenicity, Vaccine, COVID-19 Testing, Neoplasms, Immunogenetics, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], Immunology and Allergy, Humans, Immunologia, Vacunació, Registries, Immune Checkpoint Inhibitors, Pharmacology, Vaccines, Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], SARS-CoV-2, Càncer - Tractament, terapéutica::terapia biológica::inmunomodulación::inmunoterapia [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Vaccination, COVID-19, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], Cancer patients, Cellular immunity, Citotoxicitat per mediació cel·lular, Neoplasms [DISEASES], Malalts de càncer, Oncology, Molecular Medicine, Immunotherapy, Immunogenètica
Abstract: BackgroundAs management and prevention strategies against COVID-19 evolve, it is still uncertain whether prior exposure to immune checkpoint inhibitors (ICIs) affects COVID-19 severity in patients with cancer.MethodsIn a joint analysis of ICI recipients from OnCovid (NCT04393974) and European Society for Medical Oncology (ESMO) CoCARE registries, we assessed severity and mortality from SARS-CoV-2 in vaccinated and unvaccinated patients with cancer and explored whether prior immune-related adverse events (irAEs) influenced outcome from COVID-19.FindingsThe study population consisted of 240 patients diagnosed with COVID-19 between January 2020 and February 2022 exposed to ICI within 3 months prior to COVID-19 diagnosis, with a 30-day case fatality rate (CFR30) of 23.6% (95% CI 17.8 to 30.7%). Overall, 42 (17.5%) were fully vaccinated prior to COVID-19 and experienced decreased CFR30(4.8% vs 28.1%, p=0.0009), hospitalization rate (27.5% vs 63.2%, pOverall, 38 patients (15.8%) experienced at least one irAE of any grade at any time prior to COVID-19, at a median time of 3.2 months (range 0.13–48.7) from COVID-19 diagnosis. IrAEs occurred independently of baseline characteristics except for primary tumor (p=0.0373) and were associated with a significantly decreased CFR30(10.8% vs 26.0%, p=0.0462) additionally confirmed by the IPTW-fitted multivariable analysis (aOR 0.47, 95% CI 0.33 to 0.67). Patients who experienced irAEs also presented a higher median absolute lymphocyte count at COVID-19 (1.4 vs 0.8 109 cells/L, p=0.0098).ConclusionAnti-SARS-CoV-2 vaccination reduces morbidity and mortality from COVID-19 in ICI recipients. History of irAEs might identify patients with pre-existing protection from COVID-19, warranting further investigation of adaptive immune determinants of protection from SARS-CoV-2.
Published: 2022

18. COVID-19 convalescent plasma to treat hospitalised COVID-19 patients with or without underlying immunodeficiency

Author: Karine Lacombe, Thomas Hueso, Raphael Porcher, Arsène Mekinian, Thibault Chiarabini, Sophie Georgin-Lavialle, Florence Ader, Julien Saison, Guillaume Martin Blondel, Nathalie De Castro, Fabrice Bonnet, Charles Cazanave, Anne François, Pascal Morel, Olivier Hermine, Valérie Pourcher, Marc Michel, Xavier Lescure, Nora Soussi, Philippe Brun, Fanny Pommeret, Pierre-Olivier Sellier, Stella Rousset, Lionel Piroth, Jean-Marie Michot, Gabriel Baron, Xavier De Lamballerie, Xavier Mariette, Pierre-Louis Tharaux, Matthieu Resche-Rigon, Philippe Ravaud, Tabassome Simon, and Pierre Tiberghien
Abstract: Efficacy of COVID-19 convalescent plasma (CCP) in COVID-19 pneumonia is uncertain. The CORIPLASM study was an open-label, Bayesian randomised clinical trial evaluating the efficacy of CCP in patients with moderate COVID-19, including immunocompromised patients. Patients hospitalised with COVID-19 and less than 9 days since symptoms onset were assigned to receive 4 units of plasma over 2 days (≈ 840 ml)(CCP) or usual care alone (UC). Primary outcomes were the proportion of patients with a WHO-Clinical Progression Score (CPS) ≥6 on the 10-point scale on day (d) 4 and survival without ventilation or additional immunomodulatory treatment by d14. A total of 120 patients were recruited and assigned to CCP (n=60) or UC (n=60), including 22 (CCP) and 27 (UC) immunocompromised patients. Thirteen (22%) patients with CCP had a WHO-CPS ≥6 at d4 versus 8 (13%) with UC, adjusted odds ratio (aOR) 1.88 [95%CI 0.71 to 5.24]. By d14, 19 (31.6%) patients with CCP and 20 (33.3%) patients with UC had ventilation, additional immunomodulatory treatment or had died. Cumulative incidence of death was 3 (5%) with CCP and 8 (13%) with UC at d14 (aHR 0.40 [95%CI 0·10 -1·53]), and 7 (12%) with CCP and 12 (20%) with UC at d28 (aHR 0.51 [95%CI 0.20-1.32]). Subgroup analysis indicated that CCP might be associated with a lower mortality in immunocompromised patients (HR 0.37 [95%CI 0.14-0.97]). CCP treatment did not improve early outcomes in patients with moderate COVID-19 but was associated with reduced mortality in the subgroup of immunocompromised patients.
Published: 2022
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19. Bamlanivimab + etesevimab therapy induces SARS-CoV-2 immune escape mutations and secondary clinical deterioration in COVID-19 patients with B-cell malignancies

Author: Sophie Bockel, J. Colomba, C. Bigenwald, Aude Jary, S. Marot, Pierre Tiberghien, Thomas Hueso, A. Laparra, Frank Griscelli, Fanny Pommeret, Emeline Colomba, Arnaud Bayle, J-M. Michot, Fabrice Barlesi, Karine Lacombe, Laurence Albiges, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Département d'hématologie [Gustave Roussy], Department of Radiotherapy, Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Oncologie génito-urinaire, Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Microbiologie, and Département de biologie et pathologie médicales [Gustave Roussy]
Subjects: B-Lymphocytes, Mutation, 2019-20 coronavirus outbreak, Clinical Deterioration, Coronavirus disease 2019 (COVID-19), SARS-CoV-2, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immune escape, COVID-19, Hematology, medicine.disease_cause, Virology, medicine.anatomical_structure, Oncology, Neoplasms, Humans, Medicine, business, Letter to the Editor, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, B cell
Abstract: International audience
Published: 2021
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20. Determinants of the outcomes of patients with cancer infected with SARS-CoV-2: results from the Gustave Roussy cohort

Author: Antoine Hollebecque, Fabrice Barlesi, Florence Netzer, Giulia Baciarello, Jean Baptiste Micol, Ludovic Lacroix, Fanny Pommeret, Emeline Colomba, Laurence Albiges, Bertrand Gachot, Véronique Saada, Julien Hadoux, Corinne Balleyguier, Annabelle Stoclin, Mathilde Hauchecorne, Frank Griscelli, Stéphanie Foulon, Thomas Hueso, Jean-Charles Soria, Benjamin Besse, Roger Sun, Florian Scotté, Jean-Marie Michot, Christophe Willekens, Dominique Valteau-Couanet, Mansouria Merad, A. Perret, Samy Ammari, Nathalie Chaput, Arnaud Bayle, and Fabrice Andre
Subjects: Cancer Research, medicine.medical_specialty, business.industry, medicine.medical_treatment, Cancer, Immunosuppression, Disease, Malignancy, medicine.disease, Targeted therapy, Oncology, Internal medicine, Cohort, medicine, Biomarker (medicine), Hormone therapy, business
Abstract: Patients with cancer are presumed to be at increased risk of severe COVID-19 outcomes due to underlying malignancy and treatment-induced immunosuppression. Of the first 178 patients managed for COVID-19 at the Gustave Roussy Cancer Centre, 125 (70.2%) were hospitalized, 47 (26.4%) developed clinical worsening and 31 (17.4%) died. An age of over 70 years, smoking status, metastatic disease, cytotoxic chemotherapy and an Eastern Cooperative Oncology Group score of ≥2 at the last visit were the strongest determinants of increased risk of death. In multivariable analysis, the Eastern Cooperative Oncology Group score remained the only predictor of death. In contrast, immunotherapy, hormone therapy and targeted therapy did not increase clinical worsening or death risk. Biomarker studies found that C-reactive protein and lactate dehydrogenase levels were significantly associated with an increased risk of clinical worsening, while C-reactive protein and D-dimer levels were associated with an increased risk of death. COVID-19 management impacted the oncological treatment strategy, inducing a median 20 d delay in 41% of patients and adaptation of the therapeutic strategy in 30% of patients. Barlesi and colleagues describe the determinants of severe COVID-19 outcomes in patients with cancer managed at the Gustave Roussy Cancer Centre.
Published: 2020
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21. Tocilizumab, an anti-IL-6 receptor antibody, to treat COVID-19-related respiratory failure: a case report

Author: Corinne Balleyguier, Mansouria Merad, Benjamin Besse, Fanny Pommeret, Bertrand Gachot, Aurélien Marabelle, Véronique Saada, Annabelle Stoclin, Jean-Marie Michot, Laurence Albiges, Florence Netzer, Franck Griscelli, Caroline Robert, Fabrice Barlesi, and Nathalie Chaput
Subjects: Coronavirus disease 2019 (COVID-19), biology, business.industry, Hematology, medicine.disease, Pneumonia, chemistry.chemical_compound, Tocilizumab, Oncology, Respiratory failure, chemistry, Immunology, Monoclonal, medicine, biology.protein, Anti-IL-6, Antibody, business, Receptor
Published: 2020
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22. Paclitaxel with or without pazopanib for ovarian cancer relapsing during bevacizumab maintenance therapy: The GINECO randomized phase II TAPAZ study

Author: Florence Joly, Michel Fabbro, Dominique Berton, Justine Lequesne, Amélie Anota, Alicja Puszkiel, Anne Floquet, Hélène Vegas, Hugues Bourgeois, Leïla Bengrine Lefevre, Benoît You, Fanny Pommeret, Alain Lortholary, Dominique Spaeth, Anne-Claire Hardy-Bessard, Cyril Abdeddaim, Marie-Christine Kaminsky-Forrett, Michel Tod, Jean-Emmanuel Kurtz, Francesco Del Piano, Jérôme Meunier, Nadia Raban, Jérome Alexandre, Marie-Ange Mouret-Reynier, Isabelle Ray-Coquard, Magali Provansal Gross, Pierre-Emmanuel Brachet, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)
Subjects: Ovarian Neoplasms, Sulfonamides, Indazoles, Paclitaxel, [SDV]Life Sciences [q-bio], Obstetrics and Gynecology, Carcinoma, Ovarian Epithelial, Bevacizumab, Pyrimidines, Oncology, Antineoplastic Combined Chemotherapy Protocols, Humans, Female, Neoplasm Recurrence, Local
Abstract: Anti-angiogenic rechallenge with bevacizumab plus chemotherapy is effective in recurrent ovarian cancer (rOC); however, data are limited on tyrosine kinase inhibitors after progression on maintenance bevacizumab.In the randomized phase II TAPAZ trial, patients with rOC during the first year of bevacizumab maintenance therapy were assigned 2:1 to either weekly paclitaxel 65 mg/mOverall, 116 patients were randomized and treated: 79 with combination therapy and 37 with single-agent paclitaxel. Median follow-up was 13.1 months. There was no difference between treatment arms in 4-month PFS rate (61% [95% CI, 51-73%] with the combination versus 68% [95% CI, 54-85%] with paclitaxel alone), median PFS (4.9 [95% CI, 4.1-6.1] versus 5.8 [95% CI, 4.8-7.4] months, respectively) or median overall survival (13.6 versus 12.9 months, respectively). The combination was associated with more grade 3/4 toxicities (87% versus 70%, respectively) and toxicity-related paclitaxel discontinuations (22% versus 11%). Pazopanib was discontinued for toxicity in 44% of patients, most commonly for gastrointestinal and vascular events. There were two treatment-related deaths, both in the combination arm (pulmonary embolism and gastrointestinal perforation). At month 4, patient-reported outcomes deteriorated from baseline in the combination arm, particularly for abdominal/gastrointestinal symptoms, which showed a clinically important difference versus paclitaxel alone.In rOC progressing during maintenance bevacizumab, adding pazopanib to paclitaxel did not improve efficacy, increased toxicity, and compromised chemotherapy delivery.govregistration:NCT02383251.
Published: 2022
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23. Vaccination against SARS-CoV-2 protects from morbidity, mortality and sequelae from COVID19 in patients with cancer

Author: David J. Pinato, Daniela Ferrante, Juan Aguilar-Company, Mark Bower, Ramon Salazar, Oriol Mirallas, Anna Sureda, Alexia Bertuzzi, Joan Brunet, Matteo Lambertini, Clara Maluquer, Paolo Pedrazzoli, Federica Biello, Alvin J.X. Lee, Christopher C.T. Sng, Raquel Liñan, Sabrina Rossi, M.Carmen Carmona-García, Rachel Sharkey, Simeon Eremiev, Gianpiero Rizzo, Hamish DC. Bain, Tamara Yu, Claudia A. Cruz, Marta Perachino, Nadia Saoudi-Gonzalez, Roser Fort-Culillas, Kris Doonga, Laura Fox, Elisa Roldán, Federica Zoratto, Gianluca Gaidano, Isabel Ruiz-Camps, Riccardo Bruna, Andrea Patriarca, Marianne Shawe-Taylor, Vittorio Fusco, Clara Martinez-Vila, Rossana Berardi, Marco Filetti, Francesca Mazzoni, Armando Santoro, Sara Delfanti, Alessandro Parisi, Paola Queirolo, Avinash Aujayeb, Lorenza Rimassa, Aleix Prat, Josep Tabernero, Alessandra Gennari, Alessio Cortellini, Joanne S. Evans, Judith Swallow, Georgina Hanbury, Chris Chung, Meera Patel, Gino Dettorre, Diego Ottaviani, Amani Chowdhury, Alvin JX. Lee, Christopher CT. Sng, Alasdair Sinclair, Lee Cooper, Lucy Rogers, Katherine Belessiotis, Cian Murphy, Samira Bawany, Saira Khalique, Ramis Andaleeb, Alessia Dalla Pria, Thomas Newsom-Davis, Saorise Dolly, Ailsa Sita-Lumsde, Eleanor Apthorp, Eleanor Jones, Mieke Van Hemelrijck, Charlotte Moss, Beth Russell, Nikolaos Diamantis, Uma Mukherjee, Sarah Townsend, Amanda Jackson, Angela Loizidou, Martine Piccart, Roxana Reyes, Elia Segui, Javier Marco-Hernández, Margarita Viladot, David Garcia Illescas, Nadia Saoudi, MCarmen Carmona Garcia, Robert Fort-Culillas, Nadia Harbeck, Rachel Wuerstlein, Franziska Henze, Sven Mahner, Ricard Mesia, Eudald Felip, Andrea Plaja, Marc Cucurull, Francesca D’Avanzo, Lorenza Scotti, Marco Krengly, Andrea Marrari, Federica Grosso, Antonio Maconi, Marta Betti, Bruno Vincenzi, Giuseppe Tonini, Alberto Zambelli, Carlo Tondini, Vittoria Fotia, Lorenzo Chiudinelli, Michela Franchi, Michela Libertini, Rossella Bertulli, Salvatore Provenzano, Daniele Generali, Salvatore Grisanti, Alice Baggi, Valeria Tovazzi, Corrado Ficorella, Giampiero Porzio, Maristella Saponara, Raffaele Giusti, Marco Tucci, Luca Cantini, Francesco Paoloni, Annalisa Guida, Sergio Bracarda, Maria Iglesias, Ana Sanchez de Torre, Fanny Pommeret, and Emeline Colomba
Subjects: Cancer Research, COVID-19 Testing, COVID-19 Vaccines, Oncology, SARS-CoV-2, Neoplasms, Vaccination, COVID-19, Humans, Morbidity
Abstract: Although SARS-CoV-2 vaccines immunogenicity in patients with cancer has been investigated, whether they can significantly improve the severity of COVID-19 in this specific population is undefined.Capitalizing on OnCovid (NCT04393974) registry data we reported COVID-19 mortality and proxies of COVID-19 morbidity, including post-COVID-19 outcomes, according to the vaccination status of the included patients.2090 eligible patients diagnosed with COVID-19 between 02/2020 and 11/2021 were included, of whom 1930 (92.3%) unvaccinated, 91 (4.4%) fully vaccinated and 69 (3.3%) partially vaccinated. With the exception of a higher prevalence of patients from the UK (p = 0.0003) and receiving systemic anticancer therapy at COVID-19 diagnosis (p = 0.0082) among fully vaccinated patients, no demographics/oncological features were associated with vaccination status. The 14-days case fatality rate (CFR) (5.5% vs 20.7%, p = 0.0004) and the 28-days CFR (13.2% vs 27.4%, p = 0.0028) demonstrated a significant improvement for fully vaccinated patients in comparison with unvaccinated patients. The receipt of prior full vaccination was also associated with reduced symptomatic COVID-19 (79.1% vs 88.5%, p = 0.0070), need of COVID-19 oriented therapy (34.9% vs 63.2%, p 0.0001), complications from COVID-19 (28.6% vs 39.4%, p = 0.0379), hospitalizations due to COVID-19 (42.2% vs 52.5%, p = 0.0007) and oxygen therapy requirement (35.7% vs 52%, p = 0.0036). Following Inverse Probability Treatment Weighting (IPTW) procedure no statistically significant difference according to the vaccination status was confirmed; however, all COVID-19 related outcomes were concordantly in favour of full vaccination. Among the 1228 (58.8%) patients who underwent a formal reassessment at participating centres after COVID-19 resolution, fully vaccinated patients experienced less sequelae than unvaccinated patients (6.7% vs 17.2%, p = 0.0320).This analysis provides initial evidence in support of the beneficial effect of SARS-CoV-2 vaccines against morbidity and mortality from COVID-19 in patients with cancer.
Published: 2022

24. Outcomes of the SARS-CoV-2 omicron (B.1.1.529) variant outbreak among vaccinated and unvaccinated patients with cancer in Europe: results from the retrospective, multicentre, OnCovid registry study

Author: David J Pinato, Juan Aguilar-Company, Daniela Ferrante, Georgina Hanbury, Mark Bower, Ramon Salazar, Oriol Mirallas, Anna Sureda, Andrea Plaja, Marc Cucurull, Ricard Mesia, Sarah Townsend, Amanda Jackson, Alessia Dalla Pria, Thomas Newsom-Davis, Jasmine Handford, Ailsa Sita-Lumsden, Eleanor Apthorp, Bruno Vincenzi, Alexia Bertuzzi, Joan Brunet, Matteo Lambertini, Clara Maluquer, Paolo Pedrazzoli, Federica Biello, Alasdair Sinclair, Samira Bawany, Saira Khalique, Sabrina Rossi, Lucy Rogers, Cian Murphy, Katherine Belessiotis, M Carmen Carmona-García, Rachel Sharkey, David García-Illescas, Gianpiero Rizzo, Marta Perachino, Nadia Saoudi-Gonzalez, Kris Doonga, Laura Fox, Elisa Roldán, Gianluca Gaidano, Isabel Ruiz-Camps, Riccardo Bruna, Andrea Patriarca, Clara Martinez-Vila, Luca Cantini, Alberto Zambelli, Raffaele Giusti, Francesca Mazzoni, Enrico Caliman, Armando Santoro, Federica Grosso, Alessandro Parisi, Paola Queirolo, Avinash Aujayeb, Lorenza Rimassa, Aleix Prat, Marco Tucci, Michela Libertini, Salvatore Grisanti, Uma Mukherjee, Nikolaos Diamantis, Vittorio Fusco, Daniele Generali, Salvatore Provenzano, Alessandra Gennari, Josep Tabernero, Alessio Cortellini, Joanne S Evans, Judith Swallow, Chris Chung, Meera Patel, Gino Dettorre, Diego Ottaviani, Amani Chowdhury, Eve Merry, Neha Chopra, Alvin JX Lee, Christopher CT Sng, Tamara Yu, Marianne Shawe-Taylor, Hamish DC Bain, Yien Ning Sophia Wong, Myria Galazi, Sarah Benafif, Palma Dileo, Irina Earnshaw, Grisma Patel, Anjui Wu, Gehan Soosaipillai, Lee Cooper, Ramis Andaleeb, Saoirse Dolly, Krishnie Srikandarajah, Eleanor Jones, Mieke Van Hemelrijck, Charlotte Moss, Beth Russell, John Chester, Angela Loizidou, Martine Piccart, Claudia A Cruz, Roxana Reyes, Elia Segui, Javier Marco-Hernández, Margarita Viladot, Simeon Eremiev, Roser Fort-Culillas, Isabel Garcia, Raquel Liñan, Ariadna Roqué Lloveras, Nadia Harbeck, Rachel Wuerstlein, Franziska Henze, Sven Mahner, Eudald Felip, Anna Pous, Francesca D'Avanzo, Lorenza Scotti, Marco Krengli, Andrea Marrari, Sara Delfanti, Antonio Maconi, Marta Betti, Giuseppe Tonini, Giuseppina Rita Di Fazio, Carlo Tondini, Lorenzo Chiudinelli, Michela Franchi, Rossella Bertulli, Alice Baggi, Valeria Tovazzi, Corrado Ficorella, Giampiero Porzio, Maristella Saponara, Marco Filetti, Federica Zoratto, Francesco Paoloni, Rossana Berardi, Annalisa Guida, Sergio Bracarda, Maria Iglesias, Ana Sanchez de Torre, Marco Tagliamento, Emeline Colomba, and Fanny Pommeret
Subjects: Male, SARS-CoV-2, COVID-19, Middle Aged, Disease Outbreaks, Europe, Oxygen, COVID-19 Testing, Oncology, Neoplasms, Humans, Female, Registries, Aged, Retrospective Studies
Abstract: The omicron (B.1.1.529) variant of SARS-CoV-2 is highly transmissible and escapes vaccine-induced immunity. We aimed to describe outcomes due to COVID-19 during the omicron outbreak compared with the prevaccination period and alpha (B.1.1.7) and delta (B.1.617.2) waves in patients with cancer in Europe.In this retrospective analysis of the multicentre OnCovid Registry study, we recruited patients aged 18 years or older with laboratory-confirmed diagnosis of SARS-CoV-2, who had a history of solid or haematological malignancy that was either active or in remission. Patient were recruited from 37 oncology centres from UK, Italy, Spain, France, Belgium, and Germany. Participants were followed up from COVID-19 diagnosis until death or loss to follow-up, while being treated as per standard of care. For this analysis, we excluded data from centres that did not actively enter new data after March 1, 2021 (in France, Germany, and Belgium). We compared measures of COVID-19 morbidity, which were complications from COVID-19, hospitalisation due to COVID-19, and requirement of supplemental oxygen and COVID-19-specific therapies, and COVID-19 mortality across three time periods designated as the prevaccination (Feb 27 to Nov 30, 2020), alpha-delta (Dec 1, 2020, to Dec 14, 2021), and omicron (Dec 15, 2021, to Jan 31, 2022) phases. We assessed all-cause case-fatality rates at 14 days and 28 days after diagnosis of COVID-19 overall and in unvaccinated and fully vaccinated patients and in those who received a booster dose, after adjusting for country of origin, sex, age, comorbidities, tumour type, stage, and status, and receipt of systemic anti-cancer therapy. This study is registered with ClinicalTrials.gov, NCT04393974, and is ongoing.As of Feb 4, 2022 (database lock), the registry included 3820 patients who had been diagnosed with COVID-19 between Feb 27, 2020, and Jan 31, 2022. 3473 patients were eligible for inclusion (1640 [47·4%] were women and 1822 [52·6%] were men, with a median age of 68 years [IQR 57-77]). 2033 (58·5%) of 3473 were diagnosed during the prevaccination phase, 1075 (31·0%) during the alpha-delta phase, and 365 (10·5%) during the omicron phase. Among patients diagnosed during the omicron phase, 113 (33·3%) of 339 were fully vaccinated and 165 (48·7%) were boosted, whereas among those diagnosed during the alpha-delta phase, 152 (16·6%) of 915 were fully vaccinated and 21 (2·3%) were boosted. Compared with patients diagnosed during the prevaccination period, those who were diagnosed during the omicron phase had lower case-fatality rates at 14 days (adjusted odds ratio [OR] 0·32 [95% CI 0·19-0·61) and 28 days (0·34 [0·16-0·79]), complications due to COVID-19 (0·26 [0·17-0·46]), and hospitalisation due to COVID-19 (0·17 [0·09-0·32]), and had less requirements for COVID-19-specific therapy (0·22 [0·15-0·34]) and oxygen therapy (0·24 [0·14-0·43]) than did those diagnosed during the alpha-delta phase. Unvaccinated patients diagnosed during the omicron phase had similar crude case-fatality rates at 14 days (ten [25%] of 40 patients vs 114 [17%] of 656) and at 28 days (11 [27%] of 40 vs 184 [28%] of 656) and similar rates of hospitalisation due to COVID-19 (18 [43%] of 42 vs 266 [41%] of 652) and complications from COVID-19 (13 [31%] of 42 vs 237 [36%] of 659) as those diagnosed during the alpha-delta phase.Despite time-dependent improvements in outcomes reported in the omicron phase compared with the earlier phases of the pandemic, patients with cancer remain highly susceptible to SARS-CoV-2 if they are not vaccinated against SARS-CoV-2. Our findings support universal vaccination of patients with cancer as a protective measure against morbidity and mortality from COVID-19.National Institute for Health and Care Research Imperial Biomedical Research Centre and the Cancer Treatment and Research Trust.
Published: 2022

25. Evaluation of supportive care needs, sexuality and quality of life in phase 1 trials: a prospective monocentric study

Author: Marc Hilmi, Natacha Naoun, Alice Boilève, Arthur Géraud, Arnaud Bayle, Arnaud Pagès, Marion Aupomerol, Matthieu Rouanne, François-Xavier Madec, Fanny Pommeret, Christophe Massard, Capucine Baldini, Florian Scotté, and Stéphane Champiat
Subjects: Male, Oncology, Sexual Behavior, Surveys and Questionnaires, Neoplasms, Quality of Life, Humans, Female, Prospective Studies, Sexuality
Abstract: Patients enrolled in oncology phase 1 trials (ph1) usually have advanced heavily pre-treated cancers with few therapeutic options. Quality of life (QoL) is one of the key cancer-treatment outcome measures, especially in ph1, and sexuality is an important part of Qol but rarely explored. This prospective study aims to assess supportive care needs, QoL and sexuality in ph1.Between September 2020 and June 2021, we prospectively recruited patients enrolled in ph1 at Gustave Roussy in France. Supportive care needs, QoL (EORTC QLQ-C30) and sexuality (female sexual function index for women, male sexual health questionnaire [MSHQ] for men) were assessed at baseline, one, three and 5 months. We performed multivariate analyses to identify associations between clinical characteristics, QoL and quality of sexual life over time.At baseline, we analyzed 187 patients (45% women (n = 84) and 55% men (n = 103)). Patients expressed the need for consultations in pain management, nutrition, psychology and sexology in 28%, 26%, 19% and 9%, respectively. Lower global QoL was independently associated with Royal Marsden Hospital score (p = 0.012), urogenital location tumor (p = 0.021), elevated CRP levels (p = 0.014) and pain intensity (p = 0.005). Ninety-two percent of women had sexual dysfunction. In men, a lower MSHQ score was independently associated with urogenital location tumor (p = 0.021), ECOG Performance Status (p = 0.006), comorbidity at risk (p = 0.024) and pain intensity (p = 0.004).There are significant needs for supportive care in ph1, especially in some subgroups of patients. New models of care should be developed to improve early phase pathways.
Published: 2022

26. Time-Dependent COVID-19 Mortality in Patients With Cancer: An Updated Analysis of the OnCovid Registry

Author: Gianpiero Rizzo, Eudald Felip, Annalisa Guida, Alessio Cortellini, Francesca Mazzoni, Rachel Sharkey, Alice Baggi, Emeline Colomba, Sabrina Rossi, Salvatore Grisanti, Federica Zoratto, David J. Pinato, Daniela Ferrante, Claudia Andrea Cruz, Giampero Porzio, Lorenzo Chiudinelli, Alessandra Gennari, Alexia Bertuzzi, Gianluca Gaidano, Joan Brunet, Johann Colomba, Alessia Dalla Pria, Nadia Harbeck, Raffaele Giusti, Alberto Zambelli, Angela Loizidou, Clara Martinez-Vila, Daniele Generali, Matteo Lambertini, Isabel Ruiz-Camps, Paola Queirolo, Michela Libertini, Ana Sanchez de Torre, Ailsa Sita-Lumsden, Laura Fox, Federica Biello, Javier Marco-Hernández, Nikolaos Diamantis, Elia Seguí, Lorenza Rimassa, Nadia Saoudi-Gonzalez, Ariadna Roqué Lloveras, Armando Santoro, John D. Chester, Mieke Van Hemelrijck, Carlo Tondini, Marco Krengli, Saoirse Dolly, Raquel Liñan, Elisa Roldán, Charlotte Moss, Diego Ottaviani, Fanny Pommeret, Uma Mukherjee, Andrea Patriarca, Aleix Prat, Joanne Evans, Rossana Berardi, Meera Patel, Mark Bower, Marco Tagliamento, Paolo Pedrazzoli, Juan Aguilar-Company, Lorenza Scotti, Bruno Vincenzi, Irina Earnshaw, M Carmen Carmona-García, Anna Pous, Thomas Newsom-Davis, Riccardo Bruna, Krishnie Srikandarajah, Rossella Bertulli, Josep Tabernero, Vittoria Fotia, Alessandro Parisi, Anna Sureda, Ramon Salazar, Beth Russell, Michela Franchi, Roxana Reyes, Pinato, D. J., Patel, M., Scotti, L., Colomba, E., Dolly, S., Loizidou, A., Chester, J., Mukherjee, U., Zambelli, A., Dalla Pria, A., Aguilar-Company, J., Bower, M., Salazar, R., Bertuzzi, A., Brunet, J., Lambertini, M., Tagliamento, M., Pous, A., Sita-Lumsden, A., Srikandarajah, K., Colomba, J., Pommeret, F., Segui, E., Generali, D., Grisanti, S., Pedrazzoli, P., Rizzo, G., Libertini, M., Moss, C., Evans, J. S., Russell, B., Harbeck, N., Vincenzi, B., Biello, F., Bertulli, R., Ottaviani, D., Linan, R., Rossi, S., Carmona-Garcia, M. C., Tondini, C., Fox, L., Baggi, A., Fotia, V., Parisi, A., Porzio, G., Queirolo, P., Cruz, C. A., Saoudi-Gonzalez, N., Felip, E., Roque Lloveras, A., Newsom-Davis, T., Sharkey, R., Roldan, E., Reyes, R., Zoratto, F., Earnshaw, I., Ferrante, D., Marco-Hernandez, J., Ruiz-Camps, I., Gaidano, G., Patriarca, A., Bruna, R., Sureda, A., Martinez-Vila, C., Sanchez De Torre, A., Berardi, R., Giusti, R., Mazzoni, F., Guida, A., Rimassa, L., Chiudinelli, L., Franchi, M., Krengli, M., Santoro, A., Prat, A., Tabernero, J., Van Hemelrijck, M., Diamantis, N., Gennari, A., and Cortellini, A.
Subjects: Male, Cancer Research, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), solid cancer, Internal medicine, Neoplasms, Tumor stage, COVID-19, real-world data, hematologic cancer, medicine, Humans, In patient, Registries, Pandemics, Aged, Original Investigation, business.industry, SARS-CoV-2, Hazard ratio, Outbreak, Cancer, Infant, medicine.disease, Female, Oncology, business, Case series
Abstract: IMPORTANCE Whether the severity and mortality of COVID-19 in patients with cancer have improved in terms of disease management and capacity is yet to be defined. OBJECTIVE To test whether severity and mortality from COVID-19 among patients with cancer have improved during the course of the pandemic. DESIGN, SETTING, AND PARTICIPANTS OnCovid is a European registry that collects data on consecutive patients with solid or hematologic cancer and COVID-19. This multicenter case series study included real-world data from 35 institutions across 6 countries (UK, Italy, Spain, France, Belgium, and Germany). This update included patients diagnosed between February 27, 2020, and February, 14, 2021. Inclusion criteria were confirmed diagnosis of SARS-CoV-2 infection and a history of solid or hematologic cancer. EXPOSURES SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES Deaths were differentiated at 14 days and 3 months as the 2 landmark end points. Patient characteristics and outcomes were compared by stratifying patients across 5 phases (February to March 2020, April to June 2020, July to September 2020, October to December 2020, and January to February 2021) and across 2 major outbreaks (February to June 2020 and July 2020 to February 2021). RESULTS At data cutoff, 2795 consecutive patients were included, with 2634 patients eligible for analysis (median [IQR] age, 68 [18-77] years ; 52.8% men). Eligible patients demonstrated significant time-dependent improvement in 14-day case-fatality rate (CFR) with estimates of 29.8% (95% CI, 0.26-0.33) for February to March 2020; 20.3% (95% CI, 0.17-0.23) for April to June 2020;12.5% (95% Cl, 0.06-22.90) for July to September 2020; 17.2% (95% CI, 0.15-0.21) for October to December 2020; and 14.5% (95% CI, 0.09-0.21) for January to February 2021(all P < .001) across the predefined phases. Compared with the second major outbreak, patients diagnosed in the first outbreak were more likely to be 65 years or older (974 of 1626 [60.3%] vs 564 of 1008 [56.1%]; P = .03), have at least 2 comorbidities (793 of 1626 [48.8%) vs 427 of 1008 [42.4%); P = .001), and have advanced tumors (708 of 1626 [46.4%) vs 536 of 1008 [56.1%]: P < .001). Complications of COVID-19 were more likely to be seen (738 of 1626 [45.4%) vs 342 of 1008 [33.9%]; P < .001) and require hospitalization (969 of 1626 [59.8%) vs 418 of 1008 [42.1%); P < .001) and anti-COVID-19 therapy (1004 of 1626 [61.7%) vs 501of 1008 [49.7%); P < .001) during the first major outbreak. The 14-day CFRs for the first and second major outbreaks were 25.6% (95% CI, 0.23-0.28) vs 16.2% (95% CI, 0.13-0.19; P < .001), respectively. After adjusting for country, sex, age, comorbidities, tumor stage and status, anti-COVID-19 and anticancer therapy, and COVID-19 complications, patients diagnosed in the first outbreak had an increased risk of death at 14 days (hazard ratio [HR], 1.85; 95% CI, 1.47-2.32) and 3 months (HR, 1.28; 95% CI, 1.08-1.51) compared with those diagnosed in the second outbreak. CONCLUSIONS AND RELEVANCE The findings of this registry-based study suggest that mortality in patients with cancer diagnosed with COVID-19 has improved in Europe; this improvement may be associated with earlier diagnosis, improved management, and dynamic changes in community transmission over time.
Published: 2021

27. The Polarity and Specificity of Antiviral T Lymphocyte Responses Determine Susceptibility to SARS-CoV-2 Infection in Patients with Cancer and Healthy Individuals

Author: Jean-Eudes, Fahrner, Imran, Lahmar, Anne-Gaëlle, Goubet, Yacine, Haddad, Agathe, Carrier, Marine, Mazzenga, Damien, Drubay, Carolina, Alves Costa Silva, Eric, de Sousa, Cassandra, Thelemaque, Cléa, Melenotte, Agathe, Dubuisson, Arthur, Geraud, Gladys, Ferrere, Roxanne, Birebent, Camille, Bigenwald, Marion, Picard, Luigi, Cerbone, Joana R, Lérias, Ariane, Laparra, Alice, Bernard-Tessier, Benoît, Kloeckner, Marianne, Gazzano, François-Xavier, Danlos, Safae, Terrisse, Eugenie, Pizzato, Caroline, Flament, Pierre, Ly, Eric, Tartour, Nadine, Benhamouda, Lydia, Meziani, Abdelhakim, Ahmed-Belkacem, Makoto, Miyara, Guy, Gorochov, Fabrice, Barlesi, Alexandre, Trubert, Benjamin, Ungar, Yeriel, Estrada, Caroline, Pradon, Emmanuelle, Gallois, Fanny, Pommeret, Emeline, Colomba, Pernelle, Lavaud, Marc, Deloger, Nathalie, Droin, Eric, Deutsch, Bertrand, Gachot, Jean-Philippe, Spano, Mansouria, Merad, Florian, Scotté, Aurélien, Marabelle, Frank, Griscelli, Jean-Yves, Blay, Jean-Charles, Soria, Miriam, Merad, Fabrice, André, Juliette, Villemonteix, Mathieu F, Chevalier, Sophie, Caillat-Zucman, Florence, Fenollar, Emma, Guttman-Yassky, Odile, Launay, Guido, Kroemer, Bernard, La Scola, Markus, Maeurer, Lisa, Derosa, Laurence, Zitvogel, Université Paris-Saclay, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), AP-HP. Université Paris Saclay, Prédicteurs moléculaires et nouvelles cibles en oncologie (PMNCO), and Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay
Subjects: [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, SARS-CoV-2, T-Lymphocytes, COVID-19, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Antibodies, Neutralizing, Antiviral Restriction Factors, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Oncology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Neoplasms, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Spike Glycoprotein, Coronavirus, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Abstract: Vaccination against coronavirus disease 2019 (COVID-19) relies on the in-depth understanding of protective immune responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We characterized the polarity and specificity of memory T cells directed against SARS-CoV-2 viral lysates and peptides to determine correlates with spontaneous, virus-elicited, or vaccine-induced protection against COVID-19 in disease-free and cancer-bearing individuals. A disbalance between type 1 and 2 cytokine release was associated with high susceptibility to COVID-19. Individuals susceptible to infection exhibited a specific deficit in the T helper 1/T cytotoxic 1 (Th1/Tc1) peptide repertoire affecting the receptor binding domain of the spike protein (S1-RBD), a hotspot of viral mutations. Current vaccines triggered Th1/Tc1 responses in only a fraction of all subject categories, more effectively against the original sequence of S1-RBD than that from viral variants. We speculate that the next generation of vaccines should elicit Th1/Tc1 T-cell responses against the S1-RBD domain of emerging viral variants. Significance: This study prospectively analyzed virus-specific T-cell correlates of protection against COVID-19 in healthy and cancer-bearing individuals. A disbalance between Th1/Th2 recall responses conferred susceptibility to COVID-19 in both populations, coinciding with selective defects in Th1 recognition of the receptor binding domain of spike. See related commentary by McGary and Vardhana, p. 892. This article is highlighted in the In This Issue feature, p. 873
Published: 2021
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28. Prevalence and impact of COVID-19 sequelae on treatment and survival of patients with cancer who recovered from SARS-CoV-2 infection: evidence from the OnCovid retrospective, multicentre registry study

Author: David J Pinato, Josep Tabernero, Mark Bower, Lorenza Scotti, Meera Patel, Emeline Colomba, Saoirse Dolly, Angela Loizidou, John Chester, Uma Mukherjee, Alberto Zambelli, Alessia Dalla Pria, Juan Aguilar-Company, Diego Ottaviani, Amani Chowdhury, Eve Merry, Ramon Salazar, Alexia Bertuzzi, Joan Brunet, Matteo Lambertini, Marco Tagliamento, Anna Pous, Ailsa Sita-Lumsden, Krishnie Srikandarajah, Johann Colomba, Fanny Pommeret, Elia Seguí, Daniele Generali, Salvatore Grisanti, Paolo Pedrazzoli, Gianpiero Rizzo, Michela Libertini, Charlotte Moss, Joanne S Evans, Beth Russell, Nadia Harbeck, Bruno Vincenzi, Federica Biello, Rossella Bertulli, Raquel Liñan, Sabrina Rossi, Maria Carmen Carmona-García, Carlo Tondini, Laura Fox, Alice Baggi, Vittoria Fotia, Alessandro Parisi, Giampero Porzio, Maristella Saponara, Claudia Andrea Cruz, David García-Illescas, Eudald Felip, Ariadna Roqué Lloveras, Rachel Sharkey, Elisa Roldán, Roxana Reyes, Irina Earnshaw, Daniela Ferrante, Javier Marco-Hernández, Isabel Ruiz-Camps, Gianluca Gaidano, Andrea Patriarca, Riccardo Bruna, Anna Sureda, Clara Martinez-Vila, Ana Sanchez de Torre, Luca Cantini, Marco Filetti, Lorenza Rimassa, Lorenzo Chiudinelli, Michela Franchi, Marco Krengli, Armando Santoro, Aleix Prat, Mieke Van Hemelrijck, Nikolaos Diamantis, Thomas Newsom-Davis, Alessandra Gennari, Alessio Cortellini, Judith Swallow, Chris Chung, Gino Dettorre, Neha Chopra, Alvin JX Lee, Christopher CT Sng, Yien Ning Sophia Wong, Myria Galazi, Sarah Benafif, Palma Dileo, Grisma Patel, Anjui Wu, Alasdair Sinclair, Gehan Soosaipillai, Eleanor Jones, Amanda Jackson, Martine Piccart, Emeline Colomba-Blameble, Claudia A Cruz, Elia Segui, David Garcia Illescas, Oriol Mirallas, Anna Carbó, Isabel Garcia, Rachel Wuerstlein, Ricard Mesia, Clara Maluquer, Francesca D'Avanzo, Giuseppe Tonini, Salvatore Provenzano, Valeria Tovazzi, Corrado Ficorella, Paola Queirolo, Raffaele Giusti, Francesca Mazzoni, Federica Zoratto, Marco Tucci, Rossana Berardi, Annalisa Guida, Sergio Bracarda, Maria Iglesias, Pinato, D. J., Tabernero, J., Bower, M., Scotti, L., Patel, M., Colomba, E., Dolly, S., Loizidou, A., Chester, J., Mukherjee, U., Zambelli, A., Dalla Pria, A., Aguilar-Company, J., Ottaviani, D., Chowdhury, A., Merry, E., Salazar, R., Bertuzzi, A., Brunet, J., Lambertini, M., Tagliamento, M., Pous, A., Sita-Lumsden, A., Srikandarajah, K., Colomba, J., Pommeret, F., Segui, E., Generali, D., Grisanti, S., Pedrazzoli, P., Rizzo, G., Libertini, M., Moss, C., Evans, J. S., Russell, B., Harbeck, N., Vincenzi, B., Biello, F., Bertulli, R., Linan, R., Rossi, S., Carmona-Garcia, M. C., Tondini, C., Fox, L., Baggi, A., Fotia, V., Parisi, A., Porzio, G., Saponara, M., Cruz, C. A., Garcia-Illescas, D., Felip, E., Roque Lloveras, A., Sharkey, R., Roldan, E., Reyes, R., Earnshaw, I., Ferrante, D., Marco-Hernandez, J., Ruiz-Camps, I., Gaidano, G., Patriarca, A., Bruna, R., Sureda, A., Martinez-Vila, C., Sanchez de Torre, A., Cantini, L., Filetti, M., Rimassa, L., Chiudinelli, L., Franchi, M., Krengli, M., Santoro, A., Prat, A., Van Hemelrijck, M., Diamantis, N., Newsom-Davis, T., Gennari, A., Cortellini, A., Swallow, J., Chung, C., Dettorre, G., Chopra, N., Lee, A. J., Sng, C. C., Wong, Y. N. S., Galazi, M., Benafif, S., Dileo, P., Patel, G., Wu, A., Sinclair, A., Soosaipillai, G., Jones, E., Jackson, A., Piccart, M., Colomba-Blameble, E., Garcia Illescas, D., Mirallas, O., Carbo, A., Garcia, I., Wuerstlein, R., Mesia, R., Maluquer, C., D'Avanzo, F., Tonini, G., Provenzano, S., Tovazzi, V., Ficorella, C., Queirolo, P., Giusti, R., Mazzoni, F., Zoratto, F., Tucci, M., Berardi, R., Guida, A., Bracarda, S., and Iglesias, M.
Subjects: Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Belgium, COVID-19, Disease Progression, Female, France, Germany, Hospitalization, Humans, Italy, Kaplan-Meier Estimate, Male, Middle Aged, Neoplasms, Prevalence, Registries, Retrospective Studies, Spain, United Kingdom, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Registry study, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), OnCovid, cancer treatment, Post-Acute COVID-19 Syndrome, Internal medicine, medicine, 80 and over, In patient, business.industry, Cancer, Retrospective cohort study, Articles, medicine.disease, Oncology, Research centre, Population study, business
Abstract: Background: The medium-term and long-term impact of COVID-19 in patients with cancer is not yet known. In this study, we aimed to describe the prevalence of COVID-19 sequelae and their impact on the survival of patients with cancer. We also aimed to describe patterns of resumption and modifications of systemic anti-cancer therapy following recovery from SARS-CoV-2 infection. Methods: OnCovid is an active European registry study enrolling consecutive patients aged 18 years or older with a history of solid or haematological malignancy and who had a diagnosis of RT-PCR confirmed SARS-CoV-2 infection. For this retrospective study, patients were enrolled from 35 institutions across Belgium, France, Germany, Italy, Spain, and the UK. Patients who were diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, and entered into the registry at the point of data lock (March 1, 2021), were eligible for analysis. The present analysis was focused on COVID-19 survivors who underwent clinical reassessment at each participating institution. We documented prevalence of COVID-19 sequelae and described factors associated with their development and their association with post-COVID-19 survival, which was defined as the interval from post-COVID-19 reassessment to the patients’ death or last follow-up. We also evaluated resumption of systemic anti-cancer therapy in patients treated within 4 weeks of COVID-19 diagnosis. The OnCovid study is registered in ClinicalTrials.gov, NCT04393974. Findings: 2795 patients diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, were entered into the study by the time of the data lock on March 1, 2021. After the exclusion of ineligible patients, the final study population consisted of 2634 patients. 1557 COVID-19 survivors underwent a formal clinical reassessment after a median of 22·1 months (IQR 8·4–57·8) from cancer diagnosis and 44 days (28–329) from COVID-19 diagnosis. 234 (15·0%) patients reported COVID-19 sequelae, including respiratory symptoms (116 [49·6%]) and residual fatigue (96 [41·0%]). Sequelae were more common in men (vs women; p=0·041), patients aged 65 years or older (vs other age groups; p=0·048), patients with two or more comorbidities (vs one or none; p=0·0006), and patients with a history of smoking (vs no smoking history; p=0·0004). Sequelae were associated with hospitalisation for COVID-19 (p
Published: 2021

29. Convalescent plasma therapy for B-cell–depleted patients with protracted COVID-19

Author: Stanislas Faguer, Pierre Tiberghien, Etienne Crickx, Fanny Pommeret, David Veyer, Claire Rouzaud, Fabrice Camou, Olivier Hermine, Elie Azoulay, Pierre Gallian, Cécile Pouderoux, Deborah Eshagh, Jonathan London, Fatiha Merabet, Philippe Petua, David Boutboul, Laure Anne Raillon, Valérie Zeller, Hélène Péré, Benjamin Planquette, Jérôme Pacanowski, Adrien Joseph, Marc Michel, Martin Martinot, Matthieu Mahévas, Lucienne Chatenoud, Karine Lacombe, Anne Lise Beaumont, David Ghez, Amani Ouedrani, Tali Anne Szwebel, Arsène Mekinian, Florence Ader, Thomas Hueso, Marc Garnier, and Sébastien Clerc
Subjects: 0301 basic medicine, Clinical Trials and Observations, Immunology, Pneumonia, Viral, Context (language use), 030204 cardiovascular system & hematology, Biochemistry, Immunoglobulin G, Serology, 03 medical and health sciences, Betacoronavirus, 0302 clinical medicine, Agammaglobulinemia, medicine, Humans, Adverse effect, Pandemics, COVID-19 Serotherapy, Autoimmune disease, B-Lymphocytes, biology, business.industry, SARS-CoV-2, Brief Report, Bacterial pneumonia, Immunization, Passive, COVID-19, Cell Biology, Hematology, medicine.disease, 3. Good health, Pneumonia, 030104 developmental biology, biology.protein, Antibody, business, Coronavirus Infections
Abstract: There is a Blood Commentary on this article in this issue., Key Points As a proof of concept, COVID-19 convalescent plasma represents an interesting approach in B-cell–depleted patients with protracted COVID-19.COVID-19 convalescent plasma induces a decrease in temperature and inflammatory parameters within 1 week associated with oxygen weaning., Anti-CD20 monoclonal antibodies are widely used for the treatment of hematological malignancies or autoimmune disease but may be responsible for a secondary humoral deficiency. In the context of COVID-19 infection, this may prevent the elicitation of a specific SARS-CoV-2 antibody response. We report a series of 17 consecutive patients with profound B-cell lymphopenia and prolonged COVID-19 symptoms, negative immunoglobulin G (IgG)-IgM SARS-CoV-2 serology, and positive RNAemia measured by digital polymerase chain reaction who were treated with 4 units of COVID-19 convalescent plasma. Within 48 hours of transfusion, all but 1 patient experienced an improvement of clinical symptoms. The inflammatory syndrome abated within a week. Only 1 patient who needed mechanical ventilation for severe COVID-19 disease died of bacterial pneumonia. SARS-CoV-2 RNAemia decreased to below the sensitivity threshold in all 9 evaluated patients. In 3 patients, virus-specific T-cell responses were analyzed using T-cell enzyme-linked immunospot assay before convalescent plasma transfusion. All showed a maintained SARS-CoV-2 T-cell response and poor cross-response to other coronaviruses. No adverse event was reported. Convalescent plasma with anti–SARS-CoV-2 antibodies appears to be a very promising approach in the context of protracted COVID-19 symptoms in patients unable to mount a specific humoral response to SARS-CoV-2., Visual Abstract
Published: 2020

30. Molecular apocrine tumours in EORTC 10994/BIG 1-00 phase III study: pathological response after neoadjuvant chemotherapy and clinical outcomes

Author: Richard Iggo, Jean-Michel Picquenot, Denis Larsimont, Véronique Becette, Jonas Bergh, Gaëtan MacGrogan, Jeremy Thomas, Olivier Kerdraon, Leen Slaets, David Cameron, Fanny Pommeret, C. Poncet, Jean-Christophe Tille, Frédéric Bibeau, Hervé Bonnefoi, Alexandre Bodmer, Jean-Pierre Ghnassia, Thomas Grellety, Donnat, Martin, Validation et identification de nouvelles cibles en oncologie (VINCO), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de pathologie, UNICANCER-UNICANCER, UNICANCER, European Organisation for Research and Treatment of Cancer [Bruxelles] (EORTC), European Cancer Organisation [Bruxelles] (ECCO), Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Hôpital René HUGUENIN (Saint-Cloud), Centre René Gauducheau, CRLCC René Gauducheau, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Paul Strauss, CRLCC Paul Strauss, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Cancer Research UK Edinburgh Centre [Edinburgh, UK], University of Edinburgh-MRC Institute of Genetics and Molecular Medicine [Edinburgh] (IGMM), University of Edinburgh-Medical Research Council-Medical Research Council, Hôpitaux Universitaires de Genève (HUG), Department of Oncology-Pathology [Karolinska Institutet], Karolinska Institutet [Stockholm], Bordeaux PharmacoEpi, Inserm CIC1401, Université de Bordeaux, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié [Bordeaux], and Swiss Group for Clinical Cancer Research (SAKK)
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Receptor, ErbB-2, Concordance, medicine.medical_treatment, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, ddc:616.07, Disease-Free Survival, Article, 03 medical and health sciences, Breast cancer, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Survival rate, Chemotherapy, business.industry, Gene Expression Profiling, Apocrine, medicine.disease, Immunohistochemistry, Subtyping, 3. Good health, Cancérologie, ErbB Receptors, Survival Rate, Clinical trial, Biological sciences, Treatment Outcome, Receptors, Estrogen, Chemotherapy, Adjuvant, Receptors, Androgen, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Female, Receptors, Progesterone, business
Abstract: Background: We explored, within the EORTC10994 study, the outcomes for patients with molecular apocrine (MA) breast cancer, and defined immunohistochemistry (IHC) as androgen-receptor (AR) positive, oestrogen (ER) and progesterone (PR) negative. We also assessed the concordance between IHC and gene expression arrays (GEA) in the identification of MA cancers. Methods: Centrally assessed biopsies for AR, ER, PR, HER2 and Ki67 by IHC were classified into six subtypes: MA, triple-negative (TN) basal-like, luminal A, luminal B HER2 negative, luminal B HER2 positive and “other”. The two main objectives were the pCR rates and survival outcomes in the overall MA subtype (and further divided by HER2 status) and the remaining five subtypes. Results: IHC subtyping was obtained in 846 eligible patients. Ninety-three (11%) tumours were classified as the MA subtype. Both IHC and GEA data were available for 64 patients. In this subset, IHC concordance was 88.3% in identifying MA tumours compared with GEA. Within the MA subtype, pCR was observed in 33.3% of the patients (95% CI: 29.4–43.9) and the 5-year recurrence-free interval was 59.2% (95% CI: 48.2–68.6). Patients with MA and TN basal-like tumours have lower survival outcomes. Conclusions: Irrespective of their HER2 status, the prognosis for MA tumours remains poor and adjuvant trials evaluating anti-androgens should be considered., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2019
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31. The polarity and specificity of SARS-CoV2-specific T lymphocyte responses determine disease susceptibility

Author: Jean-Yves Blay, Cléa Melenotte, Fabrice Andre, Caroline Pradon, Agathe Carrier, Lydia Meziani, Guy Gorochov, Markus Maeurer, Carolina Alves Costa Silva, Safae Terrisse, Aurélien Marabelle, L. Cerbone, Eric De Sousa, Lisa Derosa, Joana R. Lérias, François-Xavier Danlos, Fanny Pommeret, Yacine Haddad, Florence Fenollar, Bertrand Gachot, Alice Bernard, Caroline Flament, Marianne Gazzano, Benoît Kloeckner, Florian Scotté, Anne-Gaëlle Goubet, Agathe Dubuisson, Cassandra Thelemaque, Eugenie Pizzato, Sophie Caillat-Zucman, Arthur Geraud, Fabrice Barlesi, Marine Mazzenga, Frank Griscelli, Mathieu F. Chevalier, Laurence Zitvogel, Bernard La Scola, Damien Drubay, Abdelhakim Ahmed-Belkacem, Pernelle Lavaud, Emeline Colomba, Jean-Eudes Fahrner, Gladys Ferrere, Eric Tartour, Pierre Ly, Marion Picard, Ariane Laparra, Jean-Philippe Spano, Makoto Miyara, Eric Deutsch, Mansouria Merad, Jean-Charles Soria, Imran Lahmar, Guido Kroemer, and Emmanuelle Gallois
Subjects: viruses, medicine.medical_treatment, T cell, Immunotherapy, T lymphocyte, Biology, medicine.disease_cause, Virus, Immune system, Cytokine, medicine.anatomical_structure, Immunization, Immunology, medicine, Coronavirus
Abstract: Optimal vaccination and immunotherapy against coronavirus disease COVID-19 relies on the in-depth comprehension of immune responses determining the individual susceptibility to be infected by SARS-CoV-2 and to develop severe disease. We characterized the polarity and specificity of circulating SARS-CoV-2-specific T cell responses against whole virus lysates or 186 unique peptides derived from the SARS-CoV-2 or SARS-CoV-1 ORFeome on 296 cancer-bearing and 86 cancer-free individuals who were either from the pre-COVID-19 era (67 individuals) or contemporary COVID-19-free (237 individuals) or who developed COVID-19 (78 individuals) in 2020/21. The ratio between the prototypic T helper 1 (TH1) cytokine, interleukin-2, and the prototypic T helper 2 (TH2) cytokine, interleukin-5 (IL-5), released from SARS-CoV-2-specific memory T cells measured in early 2020, among SARS-CoV-2-negative persons, was associated with the susceptibility of these individuals to develop PCR-detectable SARS-CoV-2 infection in late 2020 or 2021. Of note, T cells from individuals who recovered after SARS-CoV-2 re-infection spontaneously produced elevated levels of IL-5 and secreted the immunosuppressive TH2 cytokine interleukin-10 in response to SARS-CoV-2 lysate, suggesting that TH2 responses to SARS-CoV-2 are inadequate. Moreover, individuals susceptible to SARS-CoV-2 infection exhibited a deficit in the TH1 peptide repertoire affecting the highly mutated receptor binding domain (RBD) amino acids (331-525) of the spike protein. Finally, current vaccines successfully triggered anti-RBD specific TH1 responses in 88% healthy subjects that were negative prior to immunization. These findings indicate that COVID-19 protection relies on TH1 cell immunity against SARS-CoV-2 S1-RBD which in turn likely drives the phylogenetic escape of the virus. The next generation of COVID-19 vaccines should elicit high-avidity TH1 (rather than TH2)-like T cell responses against the RBD domain of current and emerging viral variants.
Published: 2021
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32. Prolonged SARS-CoV-2 RNA virus shedding and lymphopenia are hallmarks of COVID-19 in cancer patients with poor prognosis

Author: Alain Roulet, Nitharsshini Nirmalathasan, Annabelle Stoclin, Michaela Fontenay, Guy Gorochov, Eric Deutsch, Cléa Melenotte, Lisa Derosa, Gabriel Garcia, Mansouria Merad, Aurelien Marabelle, Benjamin Lelouvier, Eugenie Pizzato, Souad Assaad, Guido Kroemer, Oliver Kepp, Stéphanie Gentile, François-Xavier Danlos, Abdelhakim Ahmed-Belkacem, Jean-Yves Blay, Lydia Meziani, Nadia Saidani, Anne-Gaëlle Goubet, Fanny Pommeret, Carolina Alves Costa Silva, Aymeric Silvin, Bertrand Gachot, Florent Ginhoux, Fabrice Andre, Didier Raoult, Emmanuelle Gallois, Yacine Haddad, Arthur Geraud, Sébastien Cortaredona, Cassandra Thelemaque, Lea Touri, Gladys Ferrere, Sylvère Durand, Emeline Colomba, Corinne Balleyguier, Eric Solary, Bernard La Scola, Damien Drubay, Claudia Grajeda-Iglesias, Frank Griscelli, Anne Florin, Suzanne Kazandjian, Laurence Albiges, Markus Maeurer, Garett Dunsmore, Fabrice Barlesi, Makoto Miyara, Mauro Piacentini, Pierre Ly, Marion Picard, Nathalie Lassau, Caroline Flament, Florian Scotté, Agathe Dubuisson, Giuseppe Ippolito, Safae Terrisse, Jean-Eudes Fahrner, Arielle Elkrief, Bertrand Routy, Marine Mazzenga, Laurence Zitvogel, Caroline Pradon, Imran Lahmar, Jean-Charles Soria, and Fanny Aprahamian
Subjects: biology, business.industry, Lymphocyte, Cancer, RNA virus, medicine.disease_cause, biology.organism_classification, medicine.disease, Granzyme B, medicine.anatomical_structure, Immunopathology, Immunology, medicine, biology.protein, Antibody, business, CD8, Coronavirus
Abstract: Patients with cancer are at higher risk of severe coronavirus infectious disease 2019 (COVID-19), but the mechanisms underlying virus-host interactions during cancer therapies remain elusive. When comparing nasopharyngeal swabs from cancer and non-cancer patients for RT-qPCR cycle thresholds measuring acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 1063 patients (58% with cancer, 89% COVID-19+), we found that malignant disease favors the magnitude and duration of viral RNA shedding concomitant with prolonged serum elevations of type 1 IFN that anticorrelated with anti-RBD IgG antibodies. Chronic viral RNA carriers exhibited the typical immunopathology of severe COVID-19 at the early phase of infection including circulation of immature neutrophils, depletion of non-conventional monocytes and a general lymphopenia that, however, was accompanied by a rise in plasmablasts, activated follicular T helper cells, and non-naive Granzyme B+ FasL+, EomehighTCF-1high, PD-1+CD8+ Tc1 cells. Virus-induced lymphopenia worsened cancer-associated lymphocyte loss, and low lymphocyte counts correlated with chronic SARS-CoV-2 RNA shedding, COVID-19 severity and a higher risk of cancer-related death in the first and second surge of the pandemic. Lymphocyte loss correlated with significant changes in metabolites from the polyamine and biliary salt pathways as well as increased blood DNA from Enterobacteriaceae and Micrococcaceae gut family members in long term viral carriers. We surmise that cancer therapies may exacerbate the paradoxical association between lymphopenia and COVID-19-related immunopathology, and that the prevention of COVID-19-induced lymphocyte loss may reduce cancer-associated death.
Published: 2021
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33. Fourteen-day survival among older adults with severe infection with severe acute respiratory syndrome coronavirus 2 treated with corticosteroid: a cohort study

Author: Laure Gallay, Viet-Thi Tran, Elodie Perrodeau, Nicolas Vignier, Matthieu Mahevas, Francesca Bisio, Emmanuel Forestier, Francois-Xavier Lescure, François-Xavier Lescure, Thibaut Fraisse, Diane Sanderink, Bertrand Lioger, Camille Boutrou, Anne - Laure Destrem, Pascal Gicquel, Martin Martinot, Jérémie Pasquier, Jean Reuter, Helene Desmurs-Clavel, Nicolas Benech, Boris Bienvenu, Guillemette Frémont, François Goehringer, Guillaume Chapelet, Olivier Grossi, Didier Laureillard, Cyrille Gourjault, Alexandre Lahens, Célia Azoulay, Nicolas Carlier, Gianpiero Tebano, Jérôme Pacanowski, Simone Tunesi, Nadège Lemaire, Laurent Bellec, Firouze Bani-Sadr, Marie Pichenot, Kevin Alexandre, Laurie Masse, Olivier Robineau, Camille Thorey, Sophie Deriaz, Julien Saison, Marie Gousseff, Laura Goehrs, Fanny Pommeret, and Université de Paris, Centre de Recherche Epidémiologie et Statistiques (CRESS UMR 1153) (CRESS UMR 1153)
Subjects: 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, medicine.drug_class, [SDV]Life Sciences [q-bio], 030106 microbiology, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Prednisone, Internal medicine, medicine, 030212 general & internal medicine, Adverse effect, ComputingMilieux_MISCELLANEOUS, business.industry, Hazard ratio, General Medicine, medicine.disease, 3. Good health, Pneumonia, Infectious Diseases, Relative risk, Corticosteroid, business, medicine.drug, Cohort study
Abstract: Objective To assess the effectiveness of corticosteroids among older adults with coronavirus disease 2019 (COVID-19) pneumonia requiring oxygen. Methods We used routine care data from 36 hospitals in France and Luxembourg to assess the effectiveness of corticosteroids with at least 0.4 mg/kg/day equivalent prednisone (treatment group) versus standard of care (control group). Participants were adults aged 80 years or older with PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or CT scan images typical of COVID-19 pneumonia, requiring oxygen ≥3 L/min, and with an inflammatory syndrome (C-reactive protein ≥40 mg/L). The primary outcome was overall survival at day 14. In our main analysis, characteristics of patients at baseline (i.e. time when patients met all inclusion criteria) were balanced by using propensity-score inverse probability of treatment weighting. Results Among the 267 patients included in the analysis, 98 were assigned to the treatment group. Their median age was 86 years (interquartile range 83–90 years) and 95% had a SARS-CoV-2 PCR-confirmed diagnosis. In total, 43/98 (43.9%) patients in the treatment group and 84/166 (50.6%) in the control group died before day 14 (weighted hazard ratio 0.67, 95% CI 0.46–0.99). The treatment and control groups did not differ significantly for the proportion of patients discharged to home/rehabilitation at day 14 (weighted relative risk 1.12, 95% CI 0.68–1.82). Twenty-two (16.7%) patients receiving corticosteroids developed adverse events, but only 11 (6.4%) from the control group. Conclusions Corticosteroids were associated with a significant increase in the overall survival at day 14 of patients aged 80 years and older hospitalized for severe COVID-19.
Published: 2021
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34. Corticosteroids in patients hospitalized for COVID-19 pneumonia who require oxygen: observational comparative study using routine care data

Author: Viet-Thi Tran, Matthieu Mahévas, Firouze Bani-Sadr, Olivier Robineau, Thomas Perpoint, Elodie Perrodeau, Laure Gallay, Philippe Ravaud, François Goehringer, François-Xavier Lescure, Sophie Ismaël, Cédric Laouénan, Jennifer Soulier, Oriane Puéchal, Eric D’Ortenzio, Yazdan Yazdanpanah, Laurence Maulin, Stéphanie Martinez, Diane Sanderink, Pascale Fialaire, Séverine Ansart, Lucas Perez, Anne - Laure Destrem, Chloé Moulin, Pascal Gicquel, Frédéric Rivière, Martin Martinot, Mahsa Mohseni Zadeh, Tomasz Chroboczek, Thibaut Challan Belval, Lionel Piroth, Thibault Sixt, Florian Moretto, André Cabié, Jérémie Pasquier, Ornella Cabras, Marine Morrier, Jean Reuter, Thomas Henin, Pierre Braquet, Helene Desmurs-Clavel, Arnaud Hot, Boris Bienvenu, Belkacem Asselate, Nicolas Vignier, Steve Nguala, Sylvain Diamantis, Guillemette Frémont, Pierre Louis Nivose, Mathilde Thiébaut, Benjamin Lefevre, Hélène Auge, Paul le Turnier, Naila Benkalfate, Olivier Grossi, Samuel Pineau, Elisa Demonchy, Julie Merindol, Claire Durand, Nathalie Tieulié, Viviane Queyrel, Didier Laureillard, Paul Loubet, Ségolène Greffe, Nathalie Dournon, Youssouf Mohamed Kassim, Cyrille Gourjault, Alexandre Lahens, Paul Legendre, Caroline Morbieu, Matthieu Mahevas, Giovanna Melica, Jean-Daniel Levièvre, Frédéric Schlemmer, Simone Tunesi, Claire Leblanc, Anne Bourgarit-Durand, Alexandre Bleibtreu, Gianpiero Tebano, Jérôme Pacanowski, Jean-Benoit Zabbe, Mathilde Devaux, Laurent Bellec, Marine Gosset-Woimant, Céleste Lambert, Maxime Hentzien, Amélie Servettaz, Kevin Alexandre, Manuel Etienne, Romain Leguillon, Marion Dollat, Rémi Lefrancois, Anne Pouvaret, Yvon Ruch, Yannick Dieudonné, Guillaume Martin-Blondel, Xavier Boumaza, Margaux Lafaurie, Macha Tetart, Adrien Lemaignen, Nicole Ferreira-Maldent, Amélie Duréault, Marie Gousseff, Claire Chantepie, Francesca Bisio, Fanny Pommeret, Emeline Colomba Blamble, and Claire Ara Somohano
Subjects: 0301 basic medicine, Adult, Male, Microbiology (medical), medicine.medical_specialty, Adolescent, medicine.medical_treatment, Therapeutic evaluation, 030106 microbiology, Population, Severity of Illness Index, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Prednisone, Adrenal Cortex Hormones, Internal medicine, Observational study, Severity of illness, Medicine, Intubation, Corticosteroids, Humans, 030212 general & internal medicine, education, Aged, Mechanical ventilation, Aged, 80 and over, education.field_of_study, business.industry, Mortality rate, Hazard ratio, Oxygen Inhalation Therapy, COVID-19, General Medicine, Middle Aged, medicine.disease, Respiration, Artificial, COVID-19 Drug Treatment, Pneumonia, C-Reactive Protein, Infectious Diseases, Original Article, Female, business, medicine.drug
Abstract: OBJECTIVE: To assess the effectiveness of corticosteroids on outcomes of patients with COVID-19 pneumonia requiring oxygen without mechanical ventilation. METHODS: We used routine care data from 51 hospitals in France and Luxembourg to assess the effectiveness of corticosteroids at 0.8 mg/kg/day eq. prednisone (CTC group) versus standard of care (no-CTC group) among adults 18 to 80 years old with confirmed COVID-19 pneumonia requiring oxygen without mechanical ventilation. The primary outcome was intubation or death by day 28. In our main analysis, characteristics of patients at baseline (i.e., time when patients met all inclusion criteria) were balanced by using propensity-score inverse probability of treatment weighting. RESULTS: Among the 891 patients included in the analysis, 203 were assigned to the CTC group. Use of corticosteroids was not significantly associated with risk of intubation or death by day 28 (weighted hazard ratio [wHR] 0.92, 95% CI 0.61 to 1.39) or cumulative death rate (wHR 1.03, 95% CI 0.54 to 1.98). However, use of corticosteroids was associated with reduced risk of intubation or death by day 28 in the prespecified subgroups of patients requiring oxygen ≥ 3 L/min (wHR 0.50, 95% CI 0.30 to 0.85) or C-reactive protein level ≥ 100 mg/L (wHR 0.44, 95%CI 0.23 to 0.85). Number of hyperglycaemia events was higher for patients with than without corticosteroids, but number of infections was similar. CONCLUSIONS: We found no association between the use of corticosteroids and intubation or death in the broad population of patients 18 to 80 years old with COVID-19 hospitalized in non-intensive care unit settings. However, the treatment was associated with reduced risk of intubation or death for patients with ≥ 3 L/min oxygen or C-reactive protein level ≥ 100 mg/L at baseline. Further research need to confirm the right timing of corticosteroids for patients with COVID-19 requiring oxygen only.
Published: 2021
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35. Metabolomic analyses of COVID-19 patients unravel stage-dependent and prognostic biomarkers

Author: Giulia Baciarello, Guido Kroemer, Fanny Pommeret, Allan Sauvat, Eric Solary, Delphine Bredel, Nitharsshini Nirmalathasan, Agathe Dubuisson, Lisa Derosa, Annabelle Stoclin, Frank Griscelli, Mathilde Roumier, Fabrice Andre, Jean-Marie Michot, Frédéric Pène, Claudia Grajeda-Iglesias, Jean-Charles Soria, François-Xavier Danlos, Fabrice Barlesi, Jérôme Duchemin, Flore Rozenberg, Caroline Pradon, Françoise Levavasseur, Anne-Gaëlle Goubet, Julien Rohmer, Luc Mouthon, Laurence Zitvogel, Laurence Albiges, Severine Mouraud, Jean-Eudes Fahrner, Christophe Willekens, Sylvère Durand, Emeline Colomba, Aurélien Marabelle, Félix Ackerman, Syrine Ellouze, Michaela Fontenay, Georges Jourdi, Marc Vasse, Delphine Cantin, Immunologie anti-tumorale et immunothérapie des cancers (ITIC), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Métabolisme, Cancer et Immunité (CRC - UMR_S 1138), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Médecine Interne [Hôpital Foch, Suresnes] (SMI), Hôpital Foch [Suresnes], Oncologie gynécologique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre de Référence National des Syndromes Hyperéosinophiliques (CEREO), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Hémostase, Inflammation, Thrombose (HITH - U1176 Inserm - CHU Bicêtre), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Université Paris-Saclay, Université Paris-Saclay, Département de biologie et pathologie médicales [Gustave Roussy], Département de soins aigus [Gustave Roussy] (DSA), Direction de la recherche [Gustave Roussy], ANR-16-RHUS-0008,LUMIERE,LUMIERE(2016), ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), and European Project: 825410,ONCOBIOME
Subjects: Male, Cancer Research, Kynurenine pathway, Metabolite, [SDV]Life Sciences [q-bio], Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease, Pharmacology, Antibodies, Monoclonal, Humanized, Article, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Metabolomics, Tocilizumab, Intensive care, medicine, Metabolome, Humans, lcsh:QH573-671, Pneumonitis, SARS-CoV-2, business.industry, lcsh:Cytology, COVID-19, Cell Biology, Prognosis, medicine.disease, COVID-19 Drug Treatment, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, chemistry, Viral infection, Female, business, Biomarkers
Abstract: The circulating metabolome provides a snapshot of the physiological state of the organism responding to pathogenic challenges. Here we report alterations in the plasma metabolome reflecting the clinical presentation of COVID-19 patients with mild (ambulatory) diseases, moderate disease (radiologically confirmed pneumonitis, hospitalization and oxygen therapy), and critical disease (in intensive care). This analysis revealed major disease- and stage-associated shifts in the metabolome, meaning that at least 77 metabolites including amino acids, lipids, polyamines and sugars, as well as their derivatives, were altered in critical COVID-19 patient’s plasma as compared to mild COVID-19 patients. Among a uniformly moderate cohort of patients who received tocilizumab, only 10 metabolites were different among individuals with a favorable evolution as compared to those who required transfer into the intensive care unit. The elevation of one single metabolite, anthranilic acid, had a poor prognostic value, correlating with the maintenance of high interleukin-10 and -18 levels. Given that products of the kynurenine pathway including anthranilic acid have immunosuppressive properties, we speculate on the therapeutic utility to inhibit the rate-limiting enzymes of this pathway including indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase.
Published: 2021
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36. Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial

Author: Mathieu Vautier, Florence Tubach, Marion Licois, Estelle Henry, Marie-Alexandra Alyanakian, Julien Poissy, Solaya Chalal, Anne Gysembergh-Houal, Stéphanie Alary, Sophie Diemunsch, Jonathan London, Camille Petit-Hoang, Ruben Benainous, Catherine Metzger, Olivier Benveniste, Hala Semri, Charléne Jouve, Robin Dhote, johann Cailhol, Elise Morawiec, Kristina Beziriganyan, Mathieu Oberlin, Paul Legendre, Hélène François, Claire Davoine, F Louni, Myriam Virlouvet, Stéphane Renaud, Christiane Verny, Bertrand Guidet, Bob Heger, Lara Zafrani, Pierre-Louis Tharaux, Mandy Nizard, Adrien Contejean, Segolene Toquet, Ulrich Clarac, Sylviane Ravato, Gaëtan Deslée, Frédéric De Blay, Christian Richard, Raphaël Porcher, Malikhone Chansombat, Marie Lachatre, Ines Ben-Mabrouk, Matthieu Uzzan, Lauren Demerville, Amélie Servettaz, Annabelle Pourbaix, Philippe Manivet, Fanny Charbonnier, Pierre-Grégoire Guinot, Alexandre Demoule, Nicolas Champtiaux, Nicolas Belaube, Jean-Pierre Riveline, Kamil Chitour, Joseph Emmerich, Arthur Neuschwander, Mickael Henriques, Anne Hutt, Arthur Pavot, Anne Rachline, Elena Fois, Audrey Phibel, Xavier Monnet, Jean-Charles Duclos-Vallée, Félix Ackermann, Maria Pereira, Anne Sophie Korganow, Elodie Drouet, Tabassome Simon, Morgane Faure, Anne Pattyn, Aida Zahrate-Ghoul, Karine Martin, Jean-Jacques Tudesq, Gladys Aratus, Kévin Cardet, Julien Pottecher, Eric Demonsant, Arsène Mekinian, Rémy Gauzit, Julie Smati, Robin Deleris, Jean-Simon Rech, Boris Bienvenu, Nicolas Lefebvre, Elodie Baudry, Nicolas Bonnet, Alexis Régent, François Weill, Lalia Djaghout, Anne Tréhan, Isabelle Lehir, Elena Kiouris, Sophie Renet, Yasmina Mekid, Vanessa Rathouin, David Montani, Annick Tibi, Anne Blanchard, Fanette Denies, Nathalie Menage, Guillaume Becker, Valérie Camara-Clayette, Loic Kassegne, Nathalie Chavarot, Aurélie Clan Hew Wai, Jeremy Arzoine, Louise Bondeelle, Mohamad Zaidan, S Lariven, Laurent Cylly, Edouard Flamarion, Chaouki Bouras, Florence Bellenfant, Melissa Clément, Lola-Jade Palmieri, Marie hélène Pari, Lionel Galicier, Valérie Dejean, Delphine Feyeux, Naima Sguiouar, Anne Bergeron, Laurence Annonay, Anouk Walter-Petrich, Camille Knosp, Laurence Drouard, Thiziri Sadaoui, Julie Delemazure, Antoine Parrot, Carole Burger, Laurence Berard, Nicolas Gambier, Eric Marquis, Isabelle Madeleine, Gwenaël Lorillon, Matthieu Resche-Rigon, Yves Hansmann, Claire Rouzaud, Hélène Gros, Sophie Caillat-Zucman, Bernard Cholley, Celine Wilpotte, Chistophe Willekens, Lydia Suarez, Syllia Belazouz, Valérie Pourchet-Martinez, Dhiaa Meriem Hai, Olivier Collange, Paul Jaubert, Marie-Thérèse Tremorin, Nathalie Marin, Diane Le Pluart, Madona Sakkal, Juliette Djadi-Prat, Alexandre Morel, Agathe Bounhiol, Xavier Jaïs, Nicolas Meyer, Vixra Keo, Michaël Darmont, Benedicte Giroux-Leprieur, Anatole Harrois, Anne Adda, Yaël Amara, Fanny Pommeret, Antony Canellas, Matheus Vieira, Clotilde Le Tiec Le Tiec, Corinne Pernot, Bernard Goichot, Céline Louapre, Roza Rahli, Anne Jacolot, Anne Daguenel-Nguyen, Marie Dubert, Anaïs Razurel, Aurelie Sautereau, Mitja Jevnikar, Pierre Faye, Jeanne CHAUFFiER, Mathieu Jozwiak, Laurent Savale, Florence Patin, Kahina Cheref, Mélanie Dehais, Paul Michel Mertes, Caroline Morbieu, Valérie Paquet, Dominique Roulot, Giovanna Melica, Pauline Jouany, Frédéric Schlemmer, Blandine Lehmann, Pascal Martel, Tomas Urbina, Yazdan Yazdanpanah, Veronique Joly, Damien Bergerot, Claire Courtin, Benjamin Fournier, Guillaume Grailles, Asmaa Mamoune, Caroline Gaudefroy, Charlotte Kaeuffer, Bruno Crestani, Thinhinane Bariz, C Rioux, Karine Celli Lebras, Sophie Granville, Marion Bouhris, Hugues Cordel, Jean-Marie Michot, Mohamed Belloul, Nadège Lemarié, Philippe Dieudé, Sylvie Le Gac, Matthieu Mahévas, Pascal Richette, Anaïs Codorniu, Camille Rolland-Debord, Edouard Lefèvre, Sophie-Rym Hamada, Tristan Martin, Vincent Castelain, Aude Rigolet, Valentin Greigert, Gaelle Leroux, Simon Valayer, Eliane Bertrand, Eric Vicaut, Stéphane Brin, Jacques-Eric Gottenberg, Olivier Clovet, Marc Bardou, Muriel Fartoukh, Valentina Isernia, Ada Clarke, Bao Phung, Grégoire Martin de Frémont, Jeanne Meunier, Gonçalo Boleto, David Lebeaux, Hassan Tarhini, Asmaa Mabrouki, Pascaline Choinier, Etienne Canouï, Eric D'Ortenzio, Constance Guillaud, Corine Nyanou, Alexandre Moores, Linda Gimeno, Victoire De Lastours, F-Xavier Lescure, Claire Montlahuc, Sophie Georgin-Lavialle, A Soria, Xavier Mariette, Sophie Ismael, Prissile Bakouboula, Olivier Lambotte, Jérémie Zerbit, Aude Jacob, Z Julia, Nathalie Dournon, Marthe Rigal, Mireille Adda, Nathan Ebstein, Frédéric Duée, Helene Chambrin-Lauvray, Ramdane Meftali, Hélène Lafoeste, Coralie Bloch Queyrat, Sabrina Brahmi, Catherine Le Bourlout, Nicolas Noel, Emmanuelle Guillot, Hakim Tayebi, Sandrine Briois, Anne-Lise Pouliquen, Lakhdar Mameri, Sophie-Caroline Sacleux, Nathalie Rozensztajn, Lelia Escaut, Clément Jourdaine, Cédric Pierron, Marc Garnier, Yves Cohen, Abdellatif Tazi, Maxence Decavele, Paul Henri Grisot, Patrice Cacoub, Laure Allanic, Amira Benattia, Martin Siguier, Luca Semerano, Jean-Sébastien Hulot, Jean-Jacques Mourad, Sara Sambin, Miguel Alejandro Vasquez-Ibarra, Nabil Raked, Christine Lemagner, Martin Dres, Clara Campos-Vega, Tali-Anne Szwebel, Benjamin Chaigne, Emmanuel Andrès, Gabriel Steg, Frédéric Blanc, Isabelle Peigney, Catherine Fauvaux, Côme Bureau, Samira Saleh-Mghir, Julie Jambon, Pierre Dupland, Anne Lise Jegu, Mamadou Salif Cisse, Damien Roux, Moez Jallouli, Philippe Blanche, Sébastien Cavelot, Sophie Ohlmann-Caillard, Louise-Laure Mariani, Adrien Michon, Alain Wynckel, Saskia Flamand, Safaa Nemlaghi, Benjamin G. Chousterman, Geoffroy Volle, Cécile Kedzia, Fanny Domont, Lee S. Nguyen, Férial Berbour, Pierre Diemunsch, Celine Dupré, Etienne Lengliné, Claire Tantet, Gaël Leprun, Sara Virolle, Perrine Guillaume-Jugnot, Soumeya Hammal, B. Duchemann, Mathilde Le Marchand, Vincent Poindron, Victor Lancon, Ruxandra Burlacu, Guillaume Lefèvre, Kamyl Baghli, Emilia Stan, Yann Nguyen, Olivier Sanchez, Olivier Sitbon, Loren Soyez-Herkert, Fanny Defrancq, Véronique Vigna, Aurélien Guffroy, Martine Meunier, Pierre Mora, Léa Resmini, Liem Binh Luong Nguyen, Jean-Luc Diehl, Johanna Oziel, Emmanuelle Bugnet, Lamiae Grimaldi, Olivia Daconceicao, Marie Matignon, Mourad Djadel, Yasmine Messaoudi, Hassan Joumaa, Isabelle Dusanter, Sarah Benghanem, Julien Mayaux, Marc Michel, Claire Pernin, Antoine Gros, Nassim Mahtal, Philippe Benoit, Cloé Comarmond, Laurence Lecomte, Patricia Senet, Sebastien Abad, Jérôme Pacanowski, Céline Leplay, Claire Aguilar, Cédric Sublon, Jesuthasan Denis, Régis Peffault de Latour, Gabrielle Archer, Alain Fourreau, Emmanuelle Blin, Lise Bernard, Alexandra Beurton, Alexandre Buffet, Pierre Le Guen, Clairelyne Dupin, Olivier Fain, A Gervais, Marc Humbert, Yves Allenbach, Alexandre Bourgoin, Agnes Maurer, Eric Noll, Virginie Elisee, Adrien Mirouse, Cecile Larcheveque, Carine Karachi, Samy Figueiredo, Hakim Meddah, Greggory Ducrocq, Jeanne Goupil de Bouille, Awa Ndiaye, Jessica Krause le Garrec, Maxime Dougados, Yasmina Ferfar, Damien Vimpere, Olivier Olivier, Annabelle Stoclin, Jean-Louis Teboul, Ridha Belilita, Serge Bureau, Naura Gamany, Emeline Colomba, Baptiste Duceau, Philippe Ravaud, Corinne Guerin, Florence Morin, Pélagie Thibaut, Younes Keroumi, Julie Chas, Elisabeth Coupez, Laetitia Languille, Mathias Cornic, Jean-Michel Molina, Caroline Pradon, Alison Klasen, Zakaria Ait Hamou, Armand Mekontso-Dessaps, Yurdagul Uzunhan, Samir Hamiria, Anne Godier, Elsa Feredj, Nessima Yelles, Jean-Benoit Arlet, Christine Broissand, Belkacem Asselate, Jaouad Benhida, Julien Le Marec, Nawal Derridj, Laurène Deconinck, A. Dossier, Eric Oksenhendler, Eva Chatron, Lucie Aunay, Candice Estellat, Julie Fillon, Marie Antignac, Jade Ghosn, Ilias Koumis, David Schmitz, Domitille Molinari, Soraya Fellahi, Bruno Mégarbane, Aline Frazier, Ramon Junquera, Vincent Provitolo, Marie Lecronier, Dimitri Fremont, Pierrick Le Borgne, Emmanuel Weiss, Faouzi Saliba, Stéphan Pavy, Geoffrey Rossi, Chloe McAvoy, Eric Mariotte, Dorothee Vallois, Sabrine Ouamri, Pierre Tissieres, Luc Mouthon, Blandine Denis, Celine Comparon, Emmanuelle Sacco, Frédéric Pène, Marjolaine Morgand, Vasco Honsel, Laure Choupeaux, Bruno Mourvillier, Ewa Kozaliewicz, Marie-Hélène Legros, Isabelle Debrix, Gabriel Nisand, Julien Chabert, Juliette Camuset, Stéphane Jauréguiberry, Lynda Chalal, Marine Livrozet, Lucie Biard, Elodie Perrodeau, Brigitte Sabatier, Raphael Borie, Rosa Da Silva, Nathalie Costedoat-Chalumeau, Emmanuel Chatelus, Jean-Christophe Corvol, Nathalie De Castro, David Boutboul, Benjamin Planquette, Anne Claire Desbois, François Danion, Brigitte Ranque, Amélie Cransac, Marine Nadal, Coralie Gernez, Yacine Boudali, Claire Madelaine, Georgina Maalouf, Jonathan Marey, Sophie Bayer, Antoine Fayol, Souad Benarab, Luc Haudebourg, Sophie Bulifon, Claire Pacheco, Philippe Durand, Olivier Hermine, Fanny Alby-Laurent, Geoffroy Liégeon, Axelle Fuentes, Jean-Daniel Lelievre, Gilles Garcia, Céline Verstuyft Verstuyft, Marie-Aude Penet, Constance Delaugerre, Nicolas Carlier, Aurélie Durel Maurisse, Gilles Pialoux, Zeina Louis, Marion Parisey, Pascal Lim, Gaelle Clavere, Martin De Sarcus, Marie Vayssettes, Thomas Papo, Adrien Joseph, Hilario Nunes, Hanane Fodil, Solen Kernéis, Antoine Bachelard, Jacques Duranteau, Karine Lacombe, Olivia Lenoir, Mathilde Vallet, Isabelle Brindele, Robin Charreteur, Elie Azoulay, Dorothée Chopin, Aïcha Bah, Moustafa Benafla, Marie Gilbert, Matthieu Lemoine, Abolfazl Mohebbi, Mathilde Noaillon, Amina Kebir, Virginie Zarrouk, Cécile Yelnik, Benjamin Terrier, Solène Fabre, Paul Crespin, Sarah Dalibey, Thierno Dieye, Renaud Felten, Oriane Puéchal, Pernelle Vauboin, Caroline Hauw-Berlemont, Gabriel Baron, Paul Vermes, Yvon Ruch, Dominique Dautel, Tassadit Hadjam, Anne-Marie Roques, Jean-Philippe Bastard, Younes El Amine, Damien Sène, Alaki Thiemele, Catherine Boussard, Vincent Fallet, Timothee Bironne, Damien Vanhoye, Guillaume Geri, Amine Ghembaza, Bertrand Dunogue, Nadia Anguel, Laure Berton, Caroline Semaille, Thomas Volpe, Jacques Cadranel, Thomas Gorget, Julien Saussereau, Elodie Issorat, Sami Kolta, Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Porcher, Raphaël
Subjects: Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, 0302 clinical medicine, Randomized controlled trial, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, law, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, education.field_of_study, Hazard ratio, Articles, Middle Aged, Intensive care unit, Hospitals, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Hospitalization, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Treatment Outcome, [SDV.TOX]Life Sciences [q-bio]/Toxicology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, France, medicine.drug, Adult, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Critical Care, Population, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, education, Critical Care Outcomes, Aged, Mechanical ventilation, Anakinra, SARS-CoV-2, business.industry, Comment, COVID-19, Bayes Theorem, Pneumonia, medicine.disease, Respiration, Artificial, COVID-19 Drug Treatment, Clinical trial, Interleukin 1 Receptor Antagonist Protein, 030228 respiratory system, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, business, Interleukin-1
Abstract: International audience; Background: Patients with COVID-19 pneumonia have an excess of inflammation and increased concentrations of cytokines including interleukin-1 (IL-1). We aimed to determine whether anakinra, a recombinant human IL-1 receptor antagonist, could improve outcomes in patients in hospital with mild-to-moderate COVID-19 pneumonia.Methods: In this multicentre, open-label, Bayesian randomised clinical trial (CORIMUNO-ANA-1), nested within the CORIMUNO-19 cohort, we recruited patients from 16 University hospitals in France with mild-to-moderate COVID-19 pneumonia, severe acute respiratory syndrome coronavirus 2 infection confirmed by real-time RT-PCR, requiring at least 3 L/min of oxygen by mask or nasal cannula but without ventilation assistance, a score of 5 on the WHO Clinical Progression Scale (WHO-CPS), and a C-reactive protein serum concentration of more than 25 mg/L not requiring admission to the intensive care unit at admission to hospital. Eligible patients were randomly assigned (1:1) using a web-based secure centralised system, stratified by centre and blocked with varying block sizes (randomly of size two or four), to either usual care plus anakinra (200 mg twice a day on days 1-3, 100 mg twice on day 4, 100 mg once on day 5) or usual care alone. Usual care was provided at the discretion of the site clinicians. The two coprimary outcomes were the proportion of patients who had died or needed non-invasive or mechanical ventilation by day 4 (ie, a score of >5 on the WHO-CPS) and survival without need for mechanical or non-invasive ventilation (including high-flow oxygen) at day 14. All analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT04341584, and is now closed to accrual.Findings: Between April 8 and April 26, 2020, we screened 153 patients. The study was stopped early following the recommendation of the data and safety monitoring board, after the recruitment of 116 patients: 59 were assigned to the anakinra group, and 57 were assigned to the usual care group. Two patients in the usual care group withdrew consent and were not analysed. In the analysable population, the median age was 66 years (IQR 59 to 76) and 80 (70%) participants were men. In the anakinra group, 21 (36%) of 59 patients had a WHO-CPS score of more than 5 at day 4 versus 21 (38%) of 55 in the usual care group (median posterior absolute risk difference [ARD] -2·5%, 90% credible interval [CrI] -17·1 to 12·0), with a posterior probability of ARD of less than 0 (ie, anakinra better than usual care) of 61·2%. At day 14, 28 (47%; 95% CI 33 to 59) patients in the anakinra group and 28 (51%; 95% CI 36 to 62) in the usual care group needed ventilation or died, with a posterior probability of any efficacy of anakinra (hazard ratio [HR] being less than 1) of 54·5% (median posterior HR 0·97; 90% CrI 0·62 to 1·52). At day 90, 16 (27%) patients in the anakinra group and 15 (27%) in the usual care group had died. Serious adverse events occurred in 27 (46%) patients in the anakinra group and 21 (38%) in the usual care group (p=0·45).Interpretation: Anakinra did not improve outcomes in patients with mild-to-moderate COVID-19 pneumonia. Further studies are needed to assess the efficacy of anakinra in other selected groups of patients with more severe COVID-19.Funding: The Ministry of Health, Programme Hospitalier de Recherche Clinique, Foundation for Medical Research, and AP-HP Foundation.
Published: 2021
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37. Determinants of enhanced vulnerability to coronavirus disease 2019 in UK patients with cancer: a European study

Author: Elia Seguí, Nadia Saoudi-Gonzalez, Federica Biello, Rachel Wuerstlein, Andrea Marrari, Carlo Tondini, Ramon Salazar, Lorenza Rimassa, Claudia Andrea Cruz, Nikolaos Diamantis, David J. Pinato, Armando Santoro, Salvatore Grisanti, Clara Martinez-Vila, Charlotte Moss, Lorenzo Chiudinelli, Daniele Generali, M. C. Carmona-Garcia, Vittoria Fotia, Alexia Bertuzzi, Ailsa Sita-Lumsden, Angela Loizidou, Christopher C T Sng, Bruno Vincenzi, Alessandra Gennari, Aleix Prat, David García-Illescas, Chris Chung, Fanny Pommeret, Diego Ottaviani, Daniela Ferrante, Ariadna Roqué Lloveras, Joan Brunet, Johann Colomba, Joanne Evans, Uma Mukherjee, Alvin J.X. Lee, Juan Aguilar-Company, Andrea Patriarca, Myria Galazi, Gianluca Gaidano, Javier Marco-Hernández, Eudald Felip, Marco Krengli, Gianpiero Rizzo, Isabel Ruiz-Camps, Thomas Newsom-Davis, Mark Bower, John D. Chester, Saoirse Dolly, Yien N. Sophia Wong, Ricard Mesia, Michela Franchi, Michela Libertini, Alessio Cortellini, Roxana Reyes, Lorenza Scotti, Josep Tabernero, Rossella Bertulli, Oriol Mirallas, Valeria Tovazzi, Emeline Colomba-Blameble, Anna Sureda, Beth Russell, Raquel Liñan, Rachel Sharkey, Mieke Van Hemelrijck, Alberto Zambelli, Ana Sanchez de Torre, Pinato, David J., Scotti, Lorenza, Gennari, Alessandra, Colomba-Blameble, Emeline, Dolly, Saoirse, Loizidou, Angela, Chester, John, Mukherjee, Uma, Zambelli, Alberto, Aguilar-Company, Juan, Bower, Mark, Galazi, Myria, Salazar, Ramon, Bertuzzi, Alexia, Brunet, Joan, Mesia, Ricard, Sita-Lumsden, Ailsa, Colomba, Johann, Pommeret, Fanny, Seguí, Elia, Biello, Federica, Generali, Daniele, Grisanti, Salvatore, Rizzo, Gianpiero, Libertini, Michela, Moss, Charlotte, Evans, Joanne S., Russell, Beth, Wuerstlein, Rachel, Vincenzi, Bruno, Bertulli, Rossella, Ottaviani, Diego, Liñan, Raquel, Marrari, Andrea, Carmona-García, M. C., Sng, Christopher. C. T., Tondini, Carlo, Mirallas, Oriol, Tovazzi, Valeria, Fotia, Vittoria, Cruz, Claudia A., Saoudi-Gonzalez, Nadia, Felip, Eudald, R. Lloveras, Ariadna, Lee, Alvin. J. X., Newsom-Davis, Thoma, Sharkey, Rachel, Chung, Chri, García-Illescas, David, Reyes, Roxana, Sophia Wong, Yien N., Ferrante, Daniela, Marco-Hernández, Javier, Ruiz-Camps, Isabel, Gaidano, Gianluca, Patriarca, Andrea, Sureda, Anna, Martinez-Vila, Clara, Sanchez de Torre, Ana, Rimassa, Lorenza, Chiudinelli, Lorenzo, Franchi, Michela, Krengli, Marco, Santoro, Armando, Prat, Aleix, Tabernero, Josep, V. Hemelrijck, Mieke, Diamantis, Nikolao, and Cortellini, Alessio
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Epidemiology, Case fatality rate, medicine, COVID-19, Cancer, Europe, Mortality, SARS-CoV-2, UK, Mechanical ventilation, business.industry, Proportional hazards model, medicine.disease, Comorbidity, Confidence interval, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cohort, business
Abstract: Background: Despite high contagiousness and rapid spread, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to heterogeneous outcomes across affected nations. Within Europe (EU), the United Kingdom (UK) is the most severely affected country, with a death toll in excess of 100,000 as of January 2021. We aimed to compare the national impact of coronavirus disease 2019 (COVID-19) on the risk of death in UK patients with cancer versus those in continental EU. Methods: We performed a retrospective analysis of the OnCovid study database, a European registry of patients with cancer consecutively diagnosed with COVID-19 in 27 centres from 27th February to 10th September 2020. We analysed case fatality rates and risk of death at 30 days and 6 months stratified by region of origin (UK versus EU). We compared patient characteristics at baseline including oncological and COVID-19-specific therapy across UKand EU cohorts and evaluated the association of these factors with the risk of adverse out-comes in multivariable Cox regression models Findings: Compared with EU (n = 924), UK patients (n = 468) were characterised by higher case fatality rates (40.38% versus 26.5%, p < 0.0001) and higher risk of death at 30 days (haz-ard ratio [HR], 1.64 [95% confidence interval {CI}, 1.36-1.99]) and 6 months after COVID-19 diagnosis (47.64% versus 33.33%; p < 0.0001; HR, 1.59 [95% CI, 1.33-1.88]). UK patients were more often men, were of older age and have more comorbidities than EU counterparts (p < 0.01). Receipt of anticancer therapy was lower in UK than in EU patients (p < 0.001). Despite equal proportions of complicated COVID-19, rates of intensive care admission and use of mechanical ventilation, UK patients with cancer were less likely to receive anti-COVID-19 therapies including corticosteroids, antivirals and inter leukin-6 antagonists (p < 0.0001). Multivariable analyses adjusted for imbalanced prognostic factors confirmed the UK cohort to be characterised by worse risk of death at 30 days and 6 months, indepen-dent of the patient's age, gender, tumour stage and status; number of comorbidities; COVID-19 severity and receipt of anticancer and anti-COVID-19 therapy. Rates of permanent cessa-tion of anticancer therapy after COVID-19 were similar in the UK and EU cohorts. Interpretation: UK patients with cancer have been more severely impacted by the unfolding of the COVID-19 pandemic despite societal risk mitigation factors and rapid deferral of anti-cancer therapy. The increased frailty of UK patients with cancer highlights high-risk groups that should be prioritised for anti-SARS-CoV-2 vaccination. Continued evaluation of long-term outcomes is warranted. (C) 2021 Elsevier Ltd. All rights reserved.
Published: 2021

38. Prevalence and impact of COVID-19 sequelae on treatment pathways and survival of patients with cancer who recovered from SARS-Cov-2 infection: results from the OnCovid registry

Author: Pinato, David J., Josep, Tabernero, Mark, Bower, Lorenza, Scotti, Meera, Patel, Emeline, Colomba, Saoirse, Dolly, Angela, Loizidou, John, Chester, Uma, Mukherjee, Alberto, Zambelli, Alessia Dalla Pria, Juan, Aguilar-Company, Diego, Ottaviani, Amani, Chowdhury, Eve, Merry, Ramon, Salazar, Alexia, Bertuzzi, Joan, Brunet, Matteo, Lambertini, Marco, Tagliamento, Anna, Pous, Ailsa, Sita-Lumsden, Krishnie, Srikandarajah, Johann, Colomba, Fanny, Pommeret, Elia, Seguí, Daniele, Generali, Salvatore, Grisanti, Paolo, Pedrazzoli, Gianpiero, Rizzo, Michela, Libertini, Charlotte, Moss, Evans, Joanne S., Beth, Russell, Nadia, Harbeck, Bruno, Vincenzi, Federica, Biello, Rossella, Bertulli, Raquel, Liñan, Sabrina, Rossi, Carmen Carmona-García, M., Carlo, Tondini, Laura, Fox, Alice, Baggi, Vittoria, Fotia, Alessandro, Parisi, Giampero, Porzio, Maristella, Saponara, Claudia Andrea Cruz, David, García-Illescas, Eudald, Felip, Ariadna Roqué Lloveras, Rachel, Sharkey, Elisa, Roldán, Roxana, Reyes, Irina, Earnshaw, Ferrante, Daniela, Javier, Marco-Hernández, Isabel, Ruiz-Camps, Gianluca, Gaidano, Andrea, Patriarca, Riccardo, Bruna, Anna, Sureda, Clara, Martinez-Vila, Ana Sanchez de Torre, Luca, Cantini, Marco, Filetti, Lorenza, Rimassa, Lorenzo, Chiudinelli, Michela, Franchi, Krengli, Marco, Armando, Santoro, Aleix, Prat, Mieke Van Hemelrijck, Nikolaos, Diamantis, Thomas, Newsom-Davis, Alessandra, Gennari, and Alessio, Cortellini.
Subjects: ANTICANCER TREATMENTSLONG-TERMMORTALITY
Published: 2021

39. Secondary haemophagocytic lymphohistiocytosis is a rare occurrence amongst cancer patients with COVID‐19

Author: Laurence Albiges, Fanny Pommeret, David Ghez, Stéphanie Foulon, Franck Griscelli, Clémentine Bouchez, Arnaud Bayle, Thomas Hueso, Flore Salviat, Emmanuelle Gallois, Valérie Boige, and Veronique Vergé
Subjects: 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), SARS-CoV-2, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19, Cancer, Hematology, medicine.disease, Virology, Lymphohistiocytosis, Hemophagocytic, Neoplasms diagnosis, Neoplasms, Humans, Medicine, business
Published: 2020
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40. Elevated Calprotectin and Abnormal Myeloid Cell Subsets Discriminate Severe from Mild COVID-19

Author: Lisa Derosa, Severine Mouraud, Charles Dussiau, Annabelle Stoclin, Cyril Catelain, Aurélien Marabelle, Lai Guan Ng, Fanny Pommeret, Bertrand Gachot, Frank Griscelli, Aymeric Silvin, Alexia Alfaro, Nathalie Droin, Luc Mouthon, Damien Drubay, Clémence Hénon, Elise Sourdeau, Anne-Sophie Lhonneur, Véronique Saada, Muriel Andrieu, Zheng Zhang, Frédéric Pène, Laurence Zitvogel, T.-A. Szwebel, Pierre Bost, Florent Ginhoux, Anne-Gaëlle Goubet, Delphine Cantin, Nicolas Chapuis, Fabrice Andre, Carole Almire, Olivier Kosmider, Garett Dunsmore, Christophe Willekens, Ido Amit, Marc Deloger, Eric Solary, Chloé Friedrich, Nathalie Marin, Delphine Bredel, Philippe Rameau, Agathe Dubuisson, Didier Borderie, Fabrice Barlesi, Michaela Fontenay, Immunologie des tumeurs et immunothérapie (UMR 1015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Prédicteurs moléculaires et nouvelles cibles en oncologie (PMNCO), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre de recherche en épidémiologie et santé des populations (CESP), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay
Subjects: Myeloid, [SDV]Life Sciences [q-bio], Pneumonia, Viral, Biology, calprotectin, Monocytes, S100A9, General Biochemistry, Genetics and Molecular Biology, Article, S100A8, Flow cytometry, Betacoronavirus, 03 medical and health sciences, 0302 clinical medicine, monocyte subsets, neutrophils, medicine, Humans, Myeloid Cells, Prospective Studies, Pandemics, 030304 developmental biology, 0303 health sciences, Leukocyte L1 Antigen Complex, Innate immune system, medicine.diagnostic_test, SARS-CoV-2, COVID-19, emergency myelopoiesis, Flow Cytometry, 3. Good health, Coronavirus, medicine.anatomical_structure, Immunology, type I interferon, Myelopoiesis, Calprotectin, Coronavirus Infections, 030217 neurology & neurosurgery
Abstract: Summary Blood myeloid cells are known to be dysregulated in the coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2. It is unknown whether the innate myeloid response differs with disease severity, and whether markers of innate immunity discriminate high risk patients. Thus, we performed high dimensional flow cytometry and single cell RNA sequencing of COVID-19 patient peripheral blood cells and detected the disappearance of non-classical CD14LowCD16High monocytes, the accumulation of HLA-DRLow classical monocytes, and the release of massive amounts of calprotectin (S100A8/S100A9) in severe cases. Immature CD10LowCD101-CXCR4+/- neutrophils with an immuno-suppressive profile accumulated as well in blood and lungs, suggesting emergency myelopoiesis. We finally showed that calprotectin plasma level and a routine flow cytometry assay detecting decreased frequencies of non-classical monocytes could discriminate patients who develop a severe COVID-19 form, suggesting a predictive value that deserves prospective evaluation., Highlights • Severe patients accumulate HLA-DRLow monocytes and immature neutrophils in blood/lung. • Calprotectin level positively correlates with neutrophil count and disease severity. • Loss of non-classical monocytes could identify high risk of severe COVID-19.
Published: 2020
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41. 1688P Outcome of older cancer patients infected with COVID-19 at Gustave Roussy Cancer Center

Author: Benjamin Besse, J-C. Soria, Capucine Baldini, Fanny Pommeret, Bertrand Gachot, C. Balleyguier, Samy Ammari, Florian Scotté, Frank Griscelli, Fabrice Barlesi, Laurence Albiges, Christophe Willekens, Florence Netzer, Arnaud Bayle, Fabrice Andre, Mathilde Hauchecorne, and Stéphanie Foulon
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Anosmia, Cancer, Hematology, medicine.disease, Article, Diarrhea, Oncology, Internal medicine, Clinical endpoint, medicine, Sore throat, Thoracic ct, medicine.symptom, business
Abstract: Background: The SARS-CoV-2 outbreak significantly affected Gustave Roussy cancer center Here, we report the Gustave Roussy experience on older patients (OP) with cancer during the SARS-CoV-2 outbreak Methods: Cancer pts with suspected SARS-CoV-2 infection were admitted at Gustave Roussy starting March, 12th Screening indications have been adapted over time All the COVID-19 pts positively tested and managed at Gustave Roussy between March 14th and April 15th have been included in a redcap database Pts and underlying oncological and COVID-19 diseases characteristics have been collected Cancer and COVID-19 managements, and outcomes have been assessed The primary endpoint of this analysis was the clinical deterioration, defined as the need for O2 supplementation of 6l/min or more, or death of any cause Results: Among the first 137 cancer pts diagnosed with SARS-CoV-2, 36 patients were aged 70 years old or over (26%) Most of them were female (61%) with a median age of 75 5 years old Most frequent underlying cancers were solid tumors (92%) including GI (19%), lung (17%), GYN (14%) and head and neck (14%) Most OP (36%) were ECOG Performans status 2 versus 24% in younger patients (YP) The diagnosis of SARS-CoV-2 infection was made by RT-PCR or thoracic CT scan alone in 97% and 3% of the cases, respectively in OP and in 92% and 8% in YP Most OP experienced symptoms prior to testing (92%) compared to YP (80%) Symptoms differed according to age with more cough with sputum production in OP (14% versus 5%), dyspnea (39% versus 31%), diarrhea (17% versus 9%), shivers (8% versus 0%), sore throat (8% versus 4%) and no anosmia nor agueusia The majority of OP was hospitalized (81%) compared to 72% of YP and treated with HCQ/AZI (15;52%) compared to 25 (35%) YP with inclusion in the ONCOVID trial (EudraCT: 2020-01250-21) They did not receive any IL-6 inhibitor Only one OP was admitted in the ICU (3%) Clinical deterioration occurred in 10 OP (29%) There was no impact of age on clinical worsening (HR=1 157;95%CI 0 55-2 42;p=0 7) However age was associated with worse overall survival (OS) (HR=2 45 95%CI 1 02-5 92;p=0 0463) Results will be updated at the meeting Conclusions: OP with cancer had a different disease presentation, same rate of clinical worsening but worse OS in SARS-CoV-2 infection Legal entity responsible for the study: The authors Funding: Has not received any funding Disclosure: All authors have declared no conflicts of interest
Published: 2020
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42. Impact of young age on platinum response in women with epithelial ovarian cancer: Results of a large single-institution registry

Author: Judith Michels, Catherine Lhommé, Fanny Pommeret, Alexandra Leary, Patricia Pautier, Emilie Lanoy, Christine Larue, Gwénaël Le Teuff, Catherine Genestie, Ariane Dunant, Sebastien Gouy, Pierre Duvillard, Annie Rey, Philippe Morice, Aude Marie Savoye, Olivier Caron, Emeline Colomba, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Département de biologie et pathologie médicales [Gustave Roussy], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Oncogénétique, Gustave-Roussy, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Pôle chirurgical et interventionnel [Gustave Roussy], Institut Jean Godinot [Reims], UNICANCER, and Dr. Pautier reports support from Roche , Astra Zeneca , non-financial support from MSD , Clovis , GSK , outside the submitted work. Dr. Leary reports support from Tesaro, Clovis, Astra Zeneca, MSD, Merck Serono, Seattle Genetics , Gridstone, Biocad, Ability, Gamamabs and grants from Merus, Gamamabs, Sanofi, Inivata. Drs Michels, Genestie, Dunant, Caron, Colomba, Pommeret , Rey , Gouy , Duvillard , Le Teuff , Savoye , Lhommé , Morice report no conflict of interest.
Subjects: 0301 basic medicine, Adult, medicine.medical_specialty, endocrine system diseases, Adolescent, Organoplatinum Compounds, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Disease, Carcinoma, Ovarian Epithelial, Gastroenterology, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Epithelial ovarian cancer, Stage (cooking), Aged, Neoplasm Staging, Retrospective Studies, Aged, 80 and over, Ovarian Neoplasms, Chemotherapy, Epithelial ovarian carcinoma, business.industry, Age Factors, Obstetrics and Gynecology, Histology, Middle Aged, female genital diseases and pregnancy complications, Progression-Free Survival, 3. Good health, Survival Rate, Young age, Serous fluid, 030104 developmental biology, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Platinum resistance, Female, business, Very young woman, Rare disease, Follow-Up Studies
Abstract: International audience; Objective: In young women, EOC is a rare disease with an uncertain genetic and biological substrate. Methods: We report a long follow-up of EOC patients treated at Gustave Roussy between 1990 and 2009. We matched young patients aged ≤30 years to randomly selected older patients aged ≥40 years according to known prognostic factors (i.e. FIGO stage, histology and surgical residual disease) and the date of diagnosis with a threshold at the year 2000 to balance the treatment procedures. Results: EOC was diagnosed in 68 patients aged ≤30 years matched with 111 patients aged ≥40 years. Low-grade (LG) (i.e. serous and endometrioid) (52%, n = 35) and mucinous (i.e. 23%, n = 16 infiltrative and 12% n = 8 expansile) tumors are prevalent. High-grade (HG) tumors are rare (7%, n = 5). Early stage diseases (53%, n = 36 FIGO I/II) are predominant. Response to platinum based chemotherapy is observed to be inferior in young patients as compared to matched older patients (ORR, 29 vs 84% p = 0.0002). For HG tumors the PFS is of 0% at 5 and 10 years in younger as compared to 30% in older patients. No difference in PFS (median 4.9 vs 9.8 ms, p = 0.58) and OS (not reached vs 15.3 ms, p = 0.47) is found overall among younger and older patients respectively. The median follow-up was 72 months (range, 11–288 months). No genetic abnormalities were found. Conclusions: Young EOC patients are most often diagnosed at an early FIGO stage with LG serous or mucinous histology. Tumors are significantly more resistant to platinum-based chemotherapy in younger patients.
Published: 2020
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43. Determinants of the outcomes of patients with cancer infected with SARS-CoV-2: results from the Gustave Roussy cohort

Author: Laurence, Albiges, Stéphanie, Foulon, Arnaud, Bayle, Bertrand, Gachot, Fanny, Pommeret, Christophe, Willekens, Annabelle, Stoclin, Mansouria, Merad, Frank, Griscelli, Ludovic, Lacroix, Florence, Netzer, Thomas, Hueso, Corinne, Balleyguier, Samy, Ammari, Emeline, Colomba, Giulia, Baciarello, Audrey, Perret, Antoine, Hollebecque, Julien, Hadoux, Jean-Marie, Michot, Nathalie, Chaput, Veronique, Saada, Mathilde, Hauchecorne, Jean-Baptiste, Micol, Roger, Sun, Dominique, Valteau-Couanet, Fabrice, André, Florian, Scotte, Benjamin, Besse, Jean-Charles, Soria, and Fabrice, Barlesi
Subjects: Cohort Studies, Male, SARS-CoV-2, COVID-19, Humans, Female, Middle Aged, Aged
Abstract: Patients with cancer are presumed to be at increased risk of severe COVID-19 outcomes due to underlying malignancy and treatment-induced immunosuppression. Of the first 178 patients managed for COVID-19 at the Gustave Roussy Cancer Centre, 125 (70.2%) were hospitalized, 47 (26.4%) developed clinical worsening and 31 (17.4%) died. An age of over 70 years, smoking status, metastatic disease, cytotoxic chemotherapy and an Eastern Cooperative Oncology Group score of ≥2 at the last visit were the strongest determinants of increased risk of death. In multivariable analysis, the Eastern Cooperative Oncology Group score remained the only predictor of death. In contrast, immunotherapy, hormone therapy and targeted therapy did not increase clinical worsening or death risk. Biomarker studies found that C-reactive protein and lactate dehydrogenase levels were significantly associated with an increased risk of clinical worsening, while C-reactive protein and D-dimer levels were associated with an increased risk of death. COVID-19 management impacted the oncological treatment strategy, inducing a median 20 d delay in 41% of patients and adaptation of the therapeutic strategy in 30% of patients.
Published: 2020

44. 355 Pembrolizumab and bevacizumab in platinum resistant epithelial ovarian cancer patients

Author: Aurélien Marabelle, Christophe Massard, Fanny Pommeret, Caroline Brard, Patricia Pautier, Angelo Paci, Joseph Ciccolini, Alexandra Leary, Anne Floquet, Lauriane Eberst, Catherine Genestie, Emeline Colomba, Corinne Balleyguier, Rastilav Bahleda, Benoit You, Judith Michels, François Ghiringhelli, and Jean-Sebastien Frenel
Subjects: Pharmacology, Oncology, Cancer Research, medicine.medical_specialty, Chemotherapy, Bevacizumab, business.industry, medicine.medical_treatment, Immunology, Phases of clinical research, Cancer, Pembrolizumab, medicine.disease, Regimen, Internal medicine, medicine, Molecular Medicine, Immunology and Allergy, Ovarian cancer, Adverse effect, business, medicine.drug
Abstract: BackgroundThere is a medical need in platinum resistant ovarian cancer patients. Median progression-free survival (PFS) is 3.4 months with chemotherapy and 6.7 months with chemotherapy-bevacizumab combination regimens.1 RECIST overall response rate (ORR) is 11.8% and 27.3%, respectively. The ORR is 15.9% for bevacizumab as a monotherapy with a median PFS of 4.4 months.2MethodsNCT03596281 An open-label phase 1b trial with a modified toxicity probability interval design to evaluate the combination of a flat dose of 400mg bevacizumab for 6 cycles and 200mg pembrolizumab until disease progression, unacceptable toxicity or completed 24 months of treatment in patients with platinum resistant ovarian cancer. The primary evaluation criteria is safety, the secondary endpoint is the efficacy.Results19 patients have been enrolled between January 2019 and February 2021 in 6 French centers. Patients‘ characteristics are reported (table 1). No dose limiting toxicities were observed. Grade 3 treatment related adverse events occurred in 3 patients (i.e. arterial thromboembolism, bowel perforation, proteinuria and sepsis). No grade 4/5 toxicities were induced. A median of 7 cycles (range 3–14) were administered. Median follow-up of patients was 4.1 months (1.8–23). The RECIST ORR was 26.3% (1 complete response and 4 partial responses) (table 2). The disease control rate was 78.9%. The time to progression was not yet reached in 6 patients. The ORR was equivalent whether patients have been pretreated or not with bevacizumab (27.3 and 25% respectively) (table 3). The ORR according to the combined positive score (CPS) for the evaluation of PD-L1 was 50.0% for CPS≥10% (n=4), 30.0% for a CPS≥1% (n=10) and 25.0% for CPSConclusionsA chemotherapy-free regimen combining pembrolizumab and bevacizumab was well tolerated and showed encouraging results in heavily pretreated platinum resistant ovarian cancer patients independent of their previous challenge with antiangiogenic agents.AcknowledgementsFunding for this research was provided by Fondation Cancer du Luxembourg and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.Trial RegistrationNCT03596281ReferencesPujade-Lauraine E, et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Onco Off J Am Soc Clin Oncol 32,1302–1308 (2014).Cannistra SA, et al. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol Off J Am Soc Clin Oncol 33,5180–5186 (2007).Ethics ApprovalThis study was approved by CPP Sud Méditerranée V institution’s Ethics Board; approval number 18.020 (EudraCT number 2017-004197-34).ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.
Published: 2021
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45. 1639P Impact of COVID-19 on ongoing oncological and hematological treatment strategy

Author: M. Merad, N. Ibrahimi, Emeline Colomba, Kaissa Ouali, Florian Scotté, Samy Ammari, Arnaud Bayle, Benjamin Besse, Roger Sun, Fanny Pommeret, Stéphanie Foulon, Bertrand Gachot, Laurence Albiges, J-C. Soria, Frank Griscelli, J-M. Michot, Fabrice Barlesi, Fabrice Andre, Annabelle Stoclin, and Christophe Willekens
Subjects: Pediatrics, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, medicine.medical_treatment, Cancer, Outbreak, Hematology, Disease, medicine.disease, Intensive care unit, Article, law.invention, Radiation therapy, Oncology, law, Median follow-up, medicine, Clinical endpoint, business
Abstract: Background: Outcomes and risk factors associated with COVID-19 worsening among cancer patients have previously been reported. However, the actual impact of SARs-Co-V2 infection on the cancer treatment strategy remains unknown. Here, we report the Gustave Roussy (GR) experience, one year after the onset of the pandemic focusing on the impact of COVID-19 in patients with ongoing management of oncohematological disease. Methods: All patients positively tested for SARS-CoV-2 and managed at GR between Mar 14th 2020 and Feb 15th 2021 (data cut-off) have been included. Patients underlying oncohematological disease and COVID19 characteristics have been collected. Cancer and COVID-19 management and outcomes have been assessed. Primary endpoint was the overall impact of COVID-19 on oncological and hematological treatment strategy assessed at 1, 3, 6 and 12 months. Results: At the time of the analysis, 423 patients (median age: 62 years) were found positive for SARS-CoV-2 and managed at GR with a median follow up of 5.6 months (0-13 months). Among them, 284 (67%) were admitted due to COVID-19. Clinical deterioration occurred in 87 patients (21%), 43 patients (10%) were transferred in intensive care unit and 123 (29%) patients died, among which 47 (11%) died from COVID-19. Overall, 329 (78%) patients were on active treatment for underlying oncohematological disease at time of COVID diagnosis. Impact of COVID-19 on cancer treatment strategy in those patients is presented in the Table. The majority (N=268, 81%) had no change in oncological strategy. For those who experienced a delay, median delay in treatment was 21 days (N=99, [1-77]), 30 days (N=15, [15-56]), 7 days (N=8,[3-35]) for systemic treatment, surgery and radiotherapy respectively. [Formula presented] Conclusions: COVID-19 outbreak is associated with a significant mortality in patients with cancer. However, for patients who did not die from COVID-19, we provide the first report supporting that ongoing treatment was maintained or could be resumed in the majority of cases in a timely manner. Legal entity responsible for the study: Gustave Roussy. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Published: 2021

46. CN1 Remote monitoring by Nurses Navigators (NNs): From experimentation to optimisation of routine practices

Author: May Abbas, Florian Scotté, Fanny Pommeret, J. Legendre, Aude Fourcade, Delphine Mathivon, V. Puglisi, Olivier Mir, Etienne Minvielle, M. Di Palma, Marie Ferrua, and A. Duflot Boukobza
Subjects: Oncology, business.industry, Medicine, Hematology, Medical emergency, business, medicine.disease
Published: 2021
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47. Traitement médical du cancer de l’endomètre avancé

Author: Fanny Pommeret and Patricia Pautier
Subjects: 0301 basic medicine, 03 medical and health sciences, Cancer Research, 030104 developmental biology, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Radiology, Nuclear Medicine and imaging, Hematology, General Medicine
Abstract: Resume Le cancer de l’endometre presente generalement une evolution favorable quand il est diagnostique a un stade precoce, mais reste de mauvais pronostic en situation avancee (metastatique ou en rechute), avec peu d’options therapeutiques. L’hormonotherapie est le traitement de choix en cas de maladie lentement evolutive, et lorsque la tumeur exprime les recepteurs hormonaux. Les taxanes, les anthracyclines et les sels de platine sont les molecules de chimiotherapie les plus actives, avec des taux de reponses augmentes en cas d’association, au prix d’une toxicite non negligeable. Des therapeutiques ciblees basees sur une meilleure connaissance de la biologie tumorale sont en cours de developpement clinique, avec des resultats parfois prometteurs, surtout en association. Il est important de connaitre, pour choisir au mieux le traitement, les comorbidites associees frequentes dans cette population, les caracteristiques histologiques precises (type histologique, grade, expression des recepteurs hormonaux, et statut des proteines de reparation des mesappariements de base [statut MSI]) pour une decision therapeutique adaptee.
Published: 2017
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48. 808MO Paclitaxel with or without pazopanib in ovarian cancer patients with relapse during bevacizumab maintenance therapy: The GINECO randomized phase II TAPAZ study

Author: Cyril Abdeddaim, J. Lequesne, Dominique Spaeth, L. Bengrine Lefevre, D. Petran, Benoit You, Dominique Berton, Fanny Pommeret, Michel Fabbro, M. Cancel, F. Joly Lobbedez, M-C. Kaminsky-Forrett, Alain Lortholary, Anne Floquet, Hugues Bourgeois, Amélie Anota, J. Martin-Babau, P-E. Brachet, M. Provansal Gross, and A. Puszkiel
Subjects: Oncology, medicine.medical_specialty, Bevacizumab, business.industry, Hematology, medicine.disease, Pazopanib, chemistry.chemical_compound, Paclitaxel, chemistry, Maintenance therapy, Internal medicine, Medicine, business, Ovarian cancer, medicine.drug
Published: 2020
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49. 1694P Discovery of circulating biomarkers in COVID-19 patients undergoing anti-IL6R immunotherapy

Author: C. Escher, Fanny Pommeret, J. Rohmere, K. Kakalacheva-Beeler, M. Vasse, F.X. Danlos, E. Kishazi, Aurélien Marabelle, J-M. Michot, M. Roumier, and V. Dozio
Subjects: Oncology, medicine.medical_specialty, Multivariate analysis, business.industry, Proteomic Profiling, Disease, Hematology, medicine.disease, Article, chemistry.chemical_compound, Tocilizumab, chemistry, Intensive care, Internal medicine, Medicine, Biomarker (medicine), Personalized medicine, business, Pneumonitis
Abstract: Background: The severe pneumonitis in coronavirus disease 2019 (COVID-19) requires prolonged treatment in intensive care units, leading to overwhelmed hospital facilities Treatment with tocilizumab (Actemra, Roche), a monoclonal antibody targeting interleukin 6 receptor (IL6R), has shown promising efficacy in alleviating the severe pneumonitis However, only around 50% of the treated patients benefit from this intervention It is therefore an unmet medical need to identify biomarkers associated with the severity of disease and theranostic biomarkers to predict and differentiate potential responders from non-responders to the treatment Methods: An unbiased hyper reaction monitoring mass spectrometry (HRM™-MS) approach was used to analyze serum samples from severe COVID-19 cases before and 7 days after treatment with tocilizumab (n = 28), enabling simultaneous identification and quantification of all detectable serum proteins All samples were measured using 1h gradient on a nano-flow LC-MS/MS setup operated in data-independent acquisition (DIA) mode Data was extracted using Spectronaut™ (Biognosys) Univariate and multivariate statistical analyses were conducted to identify biomarker candidates Pathway analysis was used to identify dysregulated biological functions and signaling pathways Results: Over 450 proteins were quantified across all samples by HRM-MS Univariate statistical analysis identified significantly changing proteins across conditions (mortality day 30, pre-post treatment, responder/non-responder, q-value > 0 05 and fold change >1 5) Multivariate analysis (PLS-DA) was also used to classify proteins based on their abundance across condition Proteomic data was further integrated with clinical outcome data to identify a panel of protein biomarker candidates potentially useful in predicting tocilizumab treatment efficiency and the COVID-19 disease severity Conclusions: Unbiased proteomic profiling of COVID-19 patient serum identified a panel of candidate protein biomarkers that associate with tocilizumab treatment response as well as the ensuing course of the disease Further validation of these biomarker candidates opens the way for a personalized medicine approach in treating COVID-19 Legal entity responsible for the study: Biognosys AG Funding: Biognosys AG Disclosure: J-M Michot;F-X Danlos;F Pommeret;A Marabelle: Full/Part-time employment: Institut Gustave Roussy V Dozio;E Kishazi;C Escher;K Kakalacheva - Beeler: Full/Part-time employment: Biognosys AG M Vasse;J Rohmere;M Roumier: Full/Part-time employment: Hopital Foch
Published: 2020

50. Rucaparib in the landscape of PARP inhibition in ovarian cancer

Author: Patricia Pautier, Emeline Colomba, Alexandra Leary, and Fanny Pommeret
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Indoles, DNA Repair, DNA repair, medicine.medical_treatment, Poly ADP ribose polymerase, Antineoplastic Agents, Synthetic lethality, Poly(ADP-ribose) Polymerase Inhibitors, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Animals, Humans, Pharmacology (medical), Rucaparib, Ovarian Neoplasms, Chemotherapy, business.industry, BRCA mutation, medicine.disease, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, PARP inhibitor, Female, business, Ovarian cancer
Abstract: Introduction: The landscape of poly (ADP-ribose) polymerase (PARP) inhibition in ovarian cancer is rapidly evolving and becoming increasingly complex. Ovarian cancer is leading therapeutic innovation by providing the proof of concept for DNA repair as a target. Three different PARP inhibitors have now received approvals in the US and Europe in different indications. Subtle but crucial differences can be found among the licensed indications for each PARP inhibitor in terms of histology, type of BRCA mutation (germline and/or somatic), number of prior lines of chemotherapy and whether the indication is in the treatment or maintenance settings. Areas covered: We review the latest clinical data regarding the PARP inhibitor rucaparib in ovarian cancer, provide an update on the evolving landscape of PARP inhibition in ovarian cancer, and summarize avenues of ongoing and future research. Expert opinion: All eligible patients should be offered a PARP inhibitor. SOLO1 trial results demonstrated an unprecedented benefit maintenance with PARP inhibitors in first line. Results from trials evaluating PARP inhibitors as maintenance in first line regardless of BRCA status and from trials evaluating combinatorial strategies are eagerly awaited.
Published: 2019

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