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1. Burden of grade 3 or 4 liver injury associated with immune checkpoint inhibitors

Author

Lucia Parlati, Mehdi Sakka, Aurelia Retbi, Samir Bouam, Lamia Hassani, Jean-François Meritet, Pierre Rufat, Dominique Bonnefont-Rousselot, Rui Batista, Benoit Terris, Agnès Bellanger, Dominique Thabut, Aurore Vozy, Jean-Philippe Spano, Romain Coriat, François Goldwasser, Selim Aractingi, Philippe Sogni, Stanislas Pol, Vincent Mallet, Jérôme Alexandre, Jennifer Arrondeau, Pascaline Boudou-Rouquette, Sixtine De Percin, Nora Kramkimel, Olivier Huillard, Jeanne Chapron, Benedicte Deau-Fischer, Marie-Laure Brandely-Piat, Diane Damotte, Audrey Lupo, Marco Alifano, Marion Corouge, Clémence Hollande, Hélène Fontaine, Lorianne Lair Mehiri, Anaïs Vallet Pichard, and Patrick Tilleul

Subjects
Cancer treatment protocols, Drug-induced Liver Injury, Hepatitis, Immune checkpoint inhibitors, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background & Aims: There is concern about the burden of liver injury in patients with cancer exposed to immune checkpoints inhibitors (ICIs). Methods: In a retrospective cohort study, we evaluated the likelihood of grade 3/4 liver injury, of grade 3/4 cholestatic liver injury, and of liver failure, as per the Common Terminology Criteria for Adverse Events (CTCAE) version 5, following treatment with ICIs. We compared these occurrences with a group of cancer patients who were propensity-matched and treated with conventional chemotherapy. For all ICI patients experiencing grade 3/4 liver injury, we conducted a causality assessment using the RUCAM method and examined patient outcomes. Results: Among 952 patients (median [IQR] age 66 [57–73] years, 64% males) who were treated with ICI between January 1, 2015, and December 31, 2019, a total of 86 (9%) progressed to grade 3/4 liver injury, and liver failure was not observed. Anti-PD-(L)1/anti-CTLA-4 antibodies combinations (adjusted hazard ratio 3.36 [95% CI: 1.67–6.79]; p

Published
2023
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2. Anti-PD-1 immune-related adverse events are associated with high therapeutic antibody fixation on T cells

Author

Marianne Gazzano, Christophe Parizot, Dimitri Psimaras, Aurore Vozy, Marine Baron, Baptiste Abbar, Vincent Fallet, Elena Litvinova, Anthony Canellas, Cristina Birzu, Valérie Pourcher, Mehdi Touat, Nicolas Weiss, Sophie Demeret, Damien Roos-Weil, Jean-Philippe Spano, Celeste Lebbe, Joe-Elie Salem, Jacques Cadranel, Baptiste Hervier, Guy Gorochov, and Amélie Guihot

Subjects
biomarker, checkpoint inhibition, irAEs, immune related adverse events, flow cytometry, prediction, Immunologic diseases. Allergy, RC581-607
Abstract

Immune checkpoint inhibitors (ICI) widely improved the treatment of solid and hematologic malignancies. Yet, a remarkable proportion of patients receiving ICI develop immune related adverse events (irAEs) which are difficult to define as treatment-related. This underlines the need to develop a biomarker to guide irAE diagnosis. We developed a novel flow cytometry assay combining measurement of anti-PD-1 (programmed cell death protein-1) occupancy and evaluation of remaining PD-1 receptor availability with anti-IgG4 PE and anti-PD-1 BV421. We prospectively collected blood and biological fluids samples from patients treated by IgG4 anti-PD-1 therapy (nivolumab or pembrolizumab), with (n=18) or without (n=12) current irAE. We analyzed PD-1+ and IgG4+ staining pattern and MFI values of these parameters on CD4 and CD8 T cells, and IgG4+/PD-1+ MFI ratios are calculated. A higher mean fluorescence intensity IgG4+/PD-1+ ratio was measured on peripheral CD4+ T cells of irAE cases, when compared to controls (p=0.003). ICI-related toxicity is therefore associated with increased therapeutic antibody occupancy of PD-1 receptors on CD4+ T cells. Furthermore, in one case of ICI-related pneumonitis, binding of therapeutic antibody was stronger on lung CD4+ T cell than in blood. In another case of ICI-related encephalitis, the PD-1 receptor occupancy was total on CSF CD4 T cells, but only partial on peripherical CD4 T cells. Our results suggest that flow cytometry monitoring of ICI occupancy can be used in patients treated with monoclonal ICI to guide irAE diagnosis.

Published
2022
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3. Systemic therapies in advanced epithelioid haemangioendothelioma: A retrospective international case series from the World Sarcoma Network and a review of literature

Author

Anna M. Frezza, Vinod Ravi, Salvatore Lo Vullo, Bruno Vincenzi, Francesco Tolomeo, Tom Wei‐Wu Chen, Pawel Teterycz, Giacomo G. Baldi, Antoine Italiano, Nicolas Penel, Antonella Brunello, Florance Duffaud, Nadia Hindi, Shintaro Iwata, Alannah Smrke, Alexander Fedenko, Hans Gelderblom, Winette Van Der Graaf, Aurore Vozy, Elizabeth Connolly, Massimiliano Grassi, Robert S. Benjamin, Javier‐Martin Broto, Giovanni Grignani, Robin L. Jones, Akira Kawai, Andrzej Tysarowski, Luigi Mariani, Paolo G. Casali, and Silvia Stacchiotti

Subjects
anthracycline, chemotherapy, epithelioid haemangioendothelioma, interferon, paclitaxel, pazopanib, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background This observational, retrospective effort across Europe, US, Australia, and Asia aimed to assess the activity of systemic therapies in EHE, an ultra‐rare sarcoma, marked by WWTR1‐CAMTA1 or YAP1‐TFE3 fusions. Methods Twenty sarcoma reference centres contributed data. Patients with advanced EHE diagnosed from 2000 onwards and treated with systemic therapies, were selected. Local pathologic review and molecular confirmation were required. Radiological response was retrospectively assessed by local investigators according to RECIST. Progression free survival (PFS) and overall survival (OS) were estimated by Kaplan‐Meier method. Results Overall, 73 patients were included; 21 had more than one treatment. Thirty‐three patients received anthracyclines regimens, achieving 1 (3%) partial response (PR), 25 (76%) stable disease (SD), 7 (21%) progressive disease (PD). The median (m‐) PFS and m‐OS were 5.5 and 14.3 months respectively. Eleven patients received paclitaxel, achieving 1 (9%) PR, 6 (55%) SD, 4 (36%) PD. The m‐PFS and m‐OS were 2.9 and 18.6 months, respectively. Twelve patients received pazopanib, achieving 3 (25%) SD, 9 (75%) PD. The m‐PFS and m‐OS were.2.9 and 8.5 months, respectively. Fifteen patients received INF‐α 2b, achieving 1 (7%) PR, 11 (73%) SD, 3 (20%) PD. The m‐PFS and m‐OS were 8.9 months and 64.3, respectively. Among 27 patients treated with other regimens, 1 PR (ifosfamide) and 9 SD (5 gemcitabine +docetaxel, 2 oral cyclophosphamide, 2 others) were reported. Conclusion Systemic therapies available for advanced sarcomas have limited activity in EHE. The identification of new active compounds, especially for rapidly progressive cases, is acutely needed.

Published
2021
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4. Systemic short chain fatty acids limit antitumor effect of CTLA-4 blockade in hosts with cancer

Author

Clélia Coutzac, Jean-Mehdi Jouniaux, Angelo Paci, Julien Schmidt, Domenico Mallardo, Atmane Seck, Vahe Asvatourian, Lydie Cassard, Patrick Saulnier, Ludovic Lacroix, Paul-Louis Woerther, Aurore Vozy, Marie Naigeon, Laetitia Nebot-Bral, Mélanie Desbois, Ester Simeone, Christine Mateus, Lisa Boselli, Jonathan Grivel, Emilie Soularue, Patricia Lepage, Franck Carbonnel, Paolo Antonio Ascierto, Caroline Robert, and Nathalie Chaput

Subjects
Science
Abstract

The gut microbiota has been reported to regulate the efficacy of cancer therapy. Here, the authors show that short-chain fatty acids, which are generated through bacterial fermentation, increases immune tolerance leading to resistance to anti-CTLA-4 immunotherapy in mice and patients with metastatic melanoma.

Published
2020
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5. Reversible Tumor Progression Induced by a Dexamethasone Course for Severe COVID-19 during Immune Checkpoint Inhibitor Treatment

Author

Paul Gougis, Baptiste Abbar, Julie Benzimra, Aurore Vozy, Jean-Philippe Spano, and Luca Campedel

Subjects
immunotherapy, immune checkpoint inhibitors, COVID-19, pseudoprogression, corticosteroids, Medicine (General), R5-920
Abstract

Immunotherapies and immune checkpoint inhibitors (ICI) represent the latest revolution in oncology. Several studies have reported an association between the use of corticosteroids and poorer outcomes for patients treated with ICIs. However, it has been never established whether corticoid-induced tumor progression under ICI treatment could be reversible. We report herein transient tumor progression induced by dexamethasone for a patient treated with pembrolizumab for metastatic bladder cancer. An 82-year-old man was treated with pembrolizumab as a second-line treatment for metastatic urothelial carcinoma with stable disease for 8 months as the best tumoral response. He experienced severe coronavirus disease 2019 (COVID-19) infection and was treated with high-dose dexamethasone for ten days according to the RECOVERY protocol. Following this episode, radiological CT-scan evaluation showed tumor progression. Pembrolizumab was maintained, and subsequent radiological evaluation showed tumor shrinkage. This case highlights that the antagonistic effect of glucocorticoids with ICI efficacy is transient and can be reverted when corticoids are withdrawn. Clinicians should be aware that tumor progression in the context of the intercurrent use of systemic corticosteroids can be temporary and should be interpreted with caution, and ICI continuation could be considered for some patients. Insights: The antagonistic effect of glucocorticoids with ICI efficacy is transient and can be reverted when corticoids are withdrawn. Tumor progression in the context of the intercurrent use of systemic corticosteroids can be temporary and should be interpreted with caution, and ICI continuation could be considered for some patients.

Published
2022
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6. Cardiotoxicity Associated with Gemcitabine: Literature Review and a Pharmacovigilance Study

Author

Marc Hilmi, Stéphane Ederhy, Xavier Waintraub, Christian Funck-Brentano, Ariel Cohen, Aurore Vozy, Bénédicte Lebrun-Vignes, Javid Moslehi, Lee S. Nguyen, and Joe-Elie Salem

Subjects
gemcitabine, pericarditis, myocardial ischemia, heart failure, arrhythmias, cardio-oncology, Medicine, Pharmacy and materia medica, RS1-441
Abstract

Background: Gemcitabine is a nucleoside analog, widely used either alone or in combination, for the treatment of multiple cancers. However, gemcitabine may also be associated with cardiovascular adverse-drug-reactions (CV-ADR). Methods: First, we searched for all cases of cardiotoxicity associated with gemcitabine, published in MEDLINE on 30 May 2019. Then, we used VigiBase, the World Health Organization’s global database of individual case safety reports, to compare CV-ADR reporting associated with gemcitabine against the full database between inception and 1 April 2019. We used the information component (IC), an indicator value for disproportionate Bayesian reporting. A positive lower end of the 95% credibility interval for the IC (IC025) ≥ 0, is deemed significant. Results: In VigiBase, 46,898 reports were associated with gemcitabine on a total of 18,908,940 in the full database. Gemcitabine was associated with higher reporting for myocardial ischemia (MI, n: 119), pericardial diseases (n: 164), supraventricular arrhythmias (SVA, n: 308) and heart failure (HF, n: 484) versus full database with IC025 ranging between 0.40 and 2.81. CV-ADR were associated with cardiovascular death in up to 17% of cases. Conclusion: Treatment with gemcitabine is associated with potentially lethal CV-ADRs, including MI, pericardial diseases, SVA and HF. These events should be considered in patient care and clinical trial design.

Published
2020
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7. Abstract P2-13-02: COBRA: Characteristics and Outcomes of patients with BReast cancer in phAse I trials at Gustave Roussy Cancer center

Author

Lauren Seknazi, Arthur Geraud, Vincent Goldschmidt, Capucine Baldini, Stéphane Champiat, Christophe Massard, Sophie Postel-Vinay, Aurelien Marabelle, Rastilav Bahleda, Antoine Hollebecque, Cristina Smolenschi, Anas Gazzah, Jean-Marie Michot, Patricia Martin-Romano, Aurore Vozy, Perrine Vuagnat, François-Xavier Danlos, Arnaud Bayle, Linda Mahjoubi, Barbara Pistilli, Yohann Loriot, Santiago Ponce-Aix, and Kaissa Ouali

Subjects
Cancer Research, Oncology
Abstract

Background: Breast cancer (BC) is the most frequent cancer and the second leading cause of cancer death for women. Although there is a need of new treatments to improve BC outcome, patients with BC are still under-represented in early phase trials, possibly because of the availability of numerous approved treatments and widely recruiting phase II and III trials. We aim to characterize the molecular profile, outcome and prognostic factors of patients with BC treated in a phase I trial at our institution. Methods: We retrospectively analyzed medical records of every BC patients treated consecutively in a phase I trial in the Early Drug Development Department (DITEP) at Gustave Roussy Cancer Center. Multivariate logistic regression models were used to determine the association between known prognostic factors such as ECOG, LDH or albumin levels, number of previous lines of treatment, metastatic sites and duration of treatment. When available, molecular profile was also reviewed. Results: Between April 1st 2008 and December 31th 2021, 4682 patients were enrolled and treated in a phase I trial in our department. Among them, 272 were treated for BC (5.8%): 271 women and 1 man, in 74 different trials. The median number of BC patients treated per year was 16.5 (min 1; max 33). Median time between consented date and C1D1 was 14 days (min 1; max 63). Median age at C1D1 was 50 years old (min 24; max 82). 5 patients (1.8%) were treated in an adjuvant setting (therapeutic vaccine) while all the others were metastatic. 12 patients (4.5%) had brain metastases and 127 patients (47.6%) had liver metastases. 186 patients (70%) had only 1 or 2 metastatic sites, and 81 (30%) had three or more sites. Triple negative was the most common subtype, representing 132 patients (48.5%), 125 (46%) were ER+ and 15 (5.5%) Her2+. Patients received a median number of 3 prior lines before enrollment (min 0; max 19). Overall, only 78 patients (28%) had a genetic testing: 30.7% had a germline BRCA1/2 mutation. 146 patients (54%) had a molecular profile (liquid biopsy or tissue sample) before their enrollment and among them 32,9% were oriented in a trial according to their specific profile. Regarding the type of treatments received: 21.7% were immunotherapy, 73.6% were targeted therapies (46.7% in monotherapy, 26.9% in different combinations with immunotherapy, chemotherapy, radiotherapy or endocrine treatments), 2.9% were chemotherapy and 1.8% endocrine therapy. The overall response rate was 11.1% (0.4% complete response, 10.7% partial response, 37.5% stable disease, 43.8% progressive disease and 7.6% not evaluable). Main reasons for discontinuation of treatment were: progressive disease (80.5%), toxicity (9.6%) and end of trial (6.6%). Median duration of treatment was 2 months (min 0; max 44), only 28.6% of patients were still treated after 3 months of trial and 10% at 6 months. At data cut off (June 21st 2022) median overall survival was 11 months. All patients had discontinued the trial by the time of the analysis: median number of lines of subsequent treatment was 2 (min 0; max 10) and 31 patients (11%) were enrolled in another phase I trial in our center. In a multivariate analysis, there was no prognostic factor associated with duration of treatment whether it was albumin (p=0.76) or LDH levels (p=0.68), ECOG (p=0.67), number of prior lines of treatment (p=0.79) or number of metastatic site (p=0.05). Conclusion: These results are consistent with prior published data as only few patients with BC are addressed for inclusion in a phase I trial, despite response rates and survival rates similar to other phase I patients. We did not find any specific factor associated with duration of treatment. It is likely that a thorough molecular profile could open more treatment options and access to phase I trials. Citation Format: Lauren Seknazi, Arthur Geraud, Vincent Goldschmidt, Capucine Baldini, Stéphane Champiat, Christophe Massard, Sophie Postel-Vinay, Aurelien Marabelle, Rastilav Bahleda, Antoine Hollebecque, Cristina Smolenschi, Anas Gazzah, Jean-Marie Michot, Patricia Martin-Romano, Aurore Vozy, Perrine Vuagnat, François-Xavier Danlos, Arnaud Bayle, Linda Mahjoubi, Barbara Pistilli, Yohann Loriot, Santiago Ponce-Aix, Kaissa Ouali. COBRA: Characteristics and Outcomes of patients with BReast cancer in phAse I trials at Gustave Roussy Cancer center [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-13-02.

Published
2023

8. Liquid Biopsies for Circulating Tumor DNA Detection May Reveal Occult Hematologic Malignancies in Patients With Solid Tumors

Author

Mihaela Aldea, Marco Tagliamento, Arnaud Bayle, Damien Vasseur, Véronique Vergé, Arianna Marinello, François-Xavier Danlos, Felix Blanc-Durand, Elsa Bernard, Luigi Cerbone, Maria Fernanda Mosele, Aline Renneville, Julien Hadoux, Yohann Loriot, Madona Sakkal, Aurore Vozy, Clementine Sarkozy, Cristina Smolenschi, Claudio Nicotra, Patricia Martin-Romano, Clementine Boccon-Gibod, Wafikaamira Habza, Julien Lazarovici, Santiago Ponce, Antoine Hollebecque, Christophe Marzac, Ludovic Lacroix, Fabrice Barlesi, Fabrice André, Benjamin Besse, Etienne Rouleau, Antoine Italiano, and Jean-Baptiste Micol

Subjects
Cancer Research, Oncology
Abstract

PURPOSE High-risk clonal hematopoiesis (CH) is frequently incidentally found in patients with solid tumors undergoing plasma cell–free DNA sequencing. Here, we aimed to determine if the incidental detection of high-risk CH by liquid biopsy may reveal occult hematologic malignancies in patients with solid tumors. MATERIALS AND METHODS Adult patients with advanced solid cancers enrolled in the Gustave Roussy Cancer Profiling study (ClinicalTrials.gov identifier: NCT04932525 ) underwent at least one liquid biopsy (FoundationOne Liquid CDx). Molecular reports were discussed within the Gustave Roussy Molecular Tumor Board (MTB). Potential CH alterations were observed, and patients referred to hematology consultation in the case of pathogenic mutations in JAK2, MPL, or MYD88, irrespective of the variant allele frequency (VAF), or in DNMT3A, TET2, ASXL1, IDH1, IDH2, SF3B1, or U2AF1 with VAF ≥ 10%, while also considering patient cancer-related prognosis. TP53 mutations were discussed case-by-case. RESULTS Between March and October 2021, 1,416 patients were included. One hundred ten patients (7.7%) carried at least one high-risk CH mutation: DNMT3A (n = 32), JAK2 (n = 28), TET2 (n = 19), ASXL1 (n = 18), SF3B1 (n = 5), IDH1 (n = 4), IDH2 (n = 3), MPL (n = 3), and U2AF1 (n = 2). The MTB advised for hematologic consultation in 45 patients. Overall, 9 patients of 18 actually addressed had confirmed hematologic malignancies that were occult in six patients: two patients had myelodysplastic syndrome, two essential thrombocythemia, one a marginal lymphoma, and one a Waldenström macroglobulinemia. The other three patients were already followed up in hematology. CONCLUSION The incidental findings of high-risk CH through liquid biopsy may trigger diagnostic hematologic tests and reveal an occult hematologic malignancy. Patients should have a multidisciplinary case-by-case evaluation.

Published
2023

10. Comparaison des caractéristiques et des pronostics des patients avec et sans cancer actif hospitalisés pour une infection à SARS-CoV-2

Author

Alexandre Le Joncour, Joe-Elie Salem, Pierre Salem, Olivier Benveniste, Charlotte Fenioux, Corinne Frere, Yves Allenbach, David Saadoun, Christian Funck-Brentano, Joseph Gligorov, Patrice Cacoub, Aurore Vozy, Matheus Vieira, Luca Campedel, Paul Gougis, and Georgina Maalouf

Subjects
Male, 0301 basic medicine, Paris, Cancer Research, medicine.medical_specialty, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Population, Article Original, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Intensive care, Internal medicine, Pandemic, medicine, Humans, Cardiovascular complications, Radiology, Nuclear Medicine and imaging, Prospective Studies, education, Prospective cohort study, Pandemics, Complications cardio-vasculaires, Aged, Cancer, Aged, 80 and over, Cross Infection, education.field_of_study, business.industry, COVID-19, Hematology, General Medicine, Middle Aged, medicine.disease, Thrombosis, Hospitalization, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Female, business, Cohort study
Abstract

Introduction Les patients ayant un cancer solide ou hématologique ont été considérés comme étant plus susceptibles de contracter une infection à SARS-COV-2, et de développer plus fréquemment des complications graves. Nous avons voulu comparer les caractéristiques cliniques et le pronostic des patients atteints de COVID-19 avec ou sans cancer. Méthodes Il s’agit d’une étude observationnelle de cohorte prospective, de tous les patients hospitalisés consécutivement dans une unité dédiée aux patients atteints de COVID-19 à l’hôpital de la Pitié-Salpêtrière à Paris, entre le 16 mars et le 26 avril 2020. Résultats Parmi les 262 patients hospitalisés pour un diagnostic de COVID-19 dans cette unité lors de la première vague de la pandémie, 62 étaient également suivis pour un cancer solide ou hématologique actif. Il n’y avait pas de différence significative entre les deux groupes en ce qui concerne leurs caractéristiques cliniques, les comorbidités, ou leur pronostic entre ces deux groupes. On retrouvait cependant significativement plus de patients qui avaient une lymphopénie (médiane (IQ) : 0,7 (0,5–1,1) versus 0,9 (0,7–1,3)), et qui avaient été contaminés en milieu hospitalier (35,5 % versus 18 %, p = 0,008). Conclusions Les patients oncologiques et non oncologiques hospitalisés pour COVID-19 présentaient des résultats similaires en termes de décès, d’admission en soins intensifs ou de thrombose/hémorragie. Ils devraient bénéficier de la même stratégie thérapeutique que la population générale pendant la pandémie de COVID-19.

Published
2021

11. No Geographical Inequalities in Survival for Sarcoma Patients in France: A Reference Networks’ Outcome?

Author

Yohan Fayet, Christine Chevreau, Gauthier Decanter, Cécile Dalban, Pierre Meeus, Sébastien Carrère, Leila Haddag-Miliani, François Le Loarer, Sylvain Causeret, Daniel Orbach, Michelle Kind, Louis-Romée Le Nail, Gwenaël Ferron, Hélène Labrosse, Loïc Chaigneau, François Bertucci, Jean-Christophe Ruzic, Valérie Le Brun Ly, Fadila Farsi, Emmanuelle Bompas, Sabine Noal, Aurore Vozy, Agnes Ducoulombier, Clément Bonnet, Sylvie Chabaud, Françoise Ducimetière, Camille Tlemsani, Mickaël Ropars, Olivier Collard, Paul Michelin, Justine Gantzer, Pascale Dubray-Longeras, Maria Rios, Pauline Soibinet, Axel Le Cesne, Florence Duffaud, Marie Karanian, François Gouin, Raphaël Tétreau, Charles Honoré, Jean-Michel Coindre, Isabelle Ray-Coquard, Sylvie Bonvalot, Jean-Yves Blay, Centre Léon Bérard [Lyon], Research on Healthcare Performance (RESHAPE - Inserm U1290 - UCBL1), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, 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), Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], Institut Bergonié [Bordeaux], UNICANCER, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Institut Curie [Paris], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours (UT), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Claudius Regaud, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CHU Sud Saint Pierre [Ile de la Réunion], Hôpital Dupuytren [CHU Limoges], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Universitaire de Cancérologie [Sorbonne Université] (IUC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Galilée (Galilée), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], Cancer Research and Personalized Medicine - CARPEM [Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], 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 Paris Cité (UPCité), CHU Pontchaillou [Rennes], Université de Rennes (UR), Hôpital privé de la Loire, Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Institut de Cancérologie de Strasbourg Europe (ICANS), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre Hospitalier Universitaire de Reims (CHU Reims), Aix Marseille Université (AMU), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Lyon, Institut du Cancer de Montpellier (ICM), Pôle chirurgical et interventionnel [Gustave Roussy], Université Paris sciences et lettres (PSL), ARC Foundation [PGA1*20160203865], INCA (French National Cancer Institute) [SHSESP16-063], SIRIC LYriCAN [INCa-DGOS-Inserm_12563], INCa, DGOS, and EURACAN European Reference Network [EC 739521]

Subjects
spatial inequalities, Cancer Research, reference networks, Oncology, rare cancers, remoteness, social deprivation, France, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract

International audience; Simple Summary As patients with rare cancers face specific problems, reference networks have been developed in several European countries and then at the European level to improve their management. In some cases, the specialized centers belonging to reference networks provide remote services (specialized diagnosis review, discussion in the Multidisciplinary Tumour Board, etc.) to increase access to these services. Using data from the national sarcoma reference network implemented in France (NETSARC+), the IGeAS research program assesses the potential of its organization to address the geographical inequalities in cancer management. We analyze the individual, clinical, and geographical determinants of the overall survival of sarcoma patients in France. We found no association between the overall survival of sarcoma patients and variables measuring their social deprivation, remoteness from reference centers, and geographical context. Following previous results from the research program, this study suggests that reference network organization should be considered to reduce cancer inequalities. The national reference network NETSARC+ provides remote access to specialized diagnosis and the Multidisciplinary Tumour Board (MTB) to improve the management and survival of sarcoma patients in France. The IGeAS research program aims to assess the potential of this innovative organization to address geographical inequalities in cancer management. Using the IGeAS cohort built from the nationwide NETSARC+ database, the individual, clinical, and geographical determinants of the 3-year overall survival of sarcoma patients in France were analyzed. The survival analysis was focused on patients diagnosed in 2013 (n = 2281) to ensure sufficient hindsight to collect patient follow-up. Our study included patients with bone (16.8%), soft-tissue (69%), and visceral (14.2%) sarcomas, with a median age of 61.8 years. The overall survival was not associated with geographical variables after adjustment for individual and clinical factors. The lower survival in precarious population districts [HR 1.23, 95% CI 1.02 to 1.48] in comparison to wealthy metropolitan areas (HR = 1) found in univariable analysis was due to the worst clinical presentation at diagnosis of patients. The place of residence had no impact on sarcoma patients' survival, in the context of the national organization driven by the reference network. Following previous findings, this suggests the ability of this organization to go through geographical barriers usually impeding the optimal management of cancer patients.

Published
2022
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12. Increased reporting of fatal hepatitis associated with immune checkpoint inhibitors

Author

Douglas B. Johnson, Javid Moslehi, Joe-Elie Salem, Bénédicte Lebrun-Vignes, Eleonora De Martin, and Aurore Vozy

Subjects
Adult, Male, Cancer Research, Adolescent, Databases, Factual, Immune checkpoint inhibitors, Programmed Cell Death 1 Receptor, MEDLINE, Antibodies, Monoclonal, Humanized, World Health Organization, B7-H1 Antigen, Young Adult, Antineoplastic Agents, Immunological, Neoplasms, medicine, Humans, CTLA-4 Antigen, Young adult, Child, Aged, Aged, 80 and over, Hepatitis, biology, business.industry, Middle Aged, medicine.disease, Ipilimumab, Hepatitis, Autoimmune, Nivolumab, Oncology, Monoclonal, Immunology, biology.protein, Female, Chemical and Drug Induced Liver Injury, Antibody, Massive Hepatic Necrosis, business
Published
2019

13. High seroconversion rate but low antibody titers after two injections of BNT162b2 (Pfizer-BioNTech) vaccine in patients treated by chemotherapy for solid cancers

Author

J. Barrière, Marianne Veyri, P. Maingon, Marc-Antoine Benderra, Romain Palich, J-P. Spano, Z. Adjoutah, Laurence Morand-Joubert, A G Marcelin, Stéphane Marot, Joseph Gligorov, Aurore Vozy, Service d'Oncologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Universitaire de Cancérologie [Paris] (IUC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de virologie [CHU Pitié-Salpêtrière], Service d'Oncologie médicale [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Oncologie Radiothérapie [CHU Pitié Salpétrière], Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Cerballiance, HAL-SU, Gestionnaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Service de Virologie [CHU Pitié-Salpêtrière]

Subjects
COVID-19 Vaccines, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Neoplasms, medicine, Humans, In patient, Seroconversion, Letter to the Editor, BNT162 Vaccine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Cancer, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, Chemotherapy, Vaccines, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, business.industry, SARS-CoV-2, Vaccination, Antibody titer, COVID-19, Hematology, 3. Good health, mRNA vaccine, Serology, Oncology, 030220 oncology & carcinogenesis, Immunology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, business
Abstract

International audience

Published
2021

14. Systemic therapies in advanced epithelioid haemangioendothelioma: a retrospective international case series from the World Sarcoma Network and a review of literature

Author

Antoine Italiano, Giovanni Grignani, Luigi Mariani, Paolo G. Casali, Robin L. Jones, Massimiliano Grassi, Akira Kawai, Nicolas Penel, Aurore Vozy, Antonella Brunello, Salvatore Lo Vullo, Paweł Teterycz, Florance Duffaud, Tom Wei-Wu Chen, Francesco Tolomeo, Robert S. Benjamin, Giacomo Giulio Baldi, Andrzej Tysarowski, Bruno Vincenzi, Shintaro Iwata, Alannah Smrke, Nadia Hindi, Hans Gelderblom, Winette T. A. van der Graaf, Anna Maria Frezza, Elizabeth Connolly, Javier‐Martin Broto, Silvia Stacchiotti, Vinod Ravi, and Alexander Fedenko

Subjects
0301 basic medicine, Adult, Male, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, anthracycline, chemotherapy, lcsh:RC254-282, epithelioid haemangioendothelioma, Pazopanib, 03 medical and health sciences, paclitaxel, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, pazopanib, Humans, Radiology, Nuclear Medicine and imaging, Progression-free survival, Original Research, Retrospective Studies, Chemotherapy, Ifosfamide, business.industry, Clinical Cancer Research, International Agencies, Sarcoma, interferon, Middle Aged, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Prognosis, Gemcitabine, Survival Rate, 030104 developmental biology, Oncology, Docetaxel, 030220 oncology & carcinogenesis, Hemangioendothelioma, Epithelioid, Female, business, Progressive disease, medicine.drug, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], Follow-Up Studies
Abstract

[Background] This observational, retrospective effort across Europe, US, Australia, and Asia aimed to assess the activity of systemic therapies in EHE, an ultra-rare sarcoma, marked by WWTR1-CAMTA1 or YAP1-TFE3 fusions., [Methods] Twenty sarcoma reference centres contributed data. Patients with advanced EHE diagnosed from 2000 onwards and treated with systemic therapies, were selected. Local pathologic review and molecular confirmation were required. Radiological response was retrospectively assessed by local investigators according to RECIST. Progression free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method., [Results] Overall, 73 patients were included; 21 had more than one treatment. Thirty-three patients received anthracyclines regimens, achieving 1 (3%) partial response (PR), 25 (76%) stable disease (SD), 7 (21%) progressive disease (PD). The median (m-) PFS and m-OS were 5.5 and 14.3 months respectively. Eleven patients received paclitaxel, achieving 1 (9%) PR, 6 (55%) SD, 4 (36%) PD. The m-PFS and m-OS were 2.9 and 18.6 months, respectively. Twelve patients received pazopanib, achieving 3 (25%) SD, 9 (75%) PD. The m-PFS and m-OS were.2.9 and 8.5 months, respectively. Fifteen patients received INF-α 2b, achieving 1 (7%) PR, 11 (73%) SD, 3 (20%) PD. The m-PFS and m-OS were 8.9 months and 64.3, respectively. Among 27 patients treated with other regimens, 1 PR (ifosfamide) and 9 SD (5 gemcitabine +docetaxel, 2 oral cyclophosphamide, 2 others) were reported., [Conclusion] Systemic therapies available for advanced sarcomas have limited activity in EHE. The identification of new active compounds, especially for rapidly progressive cases, is acutely needed.

Published
2021

15. Weak immunogenicity after a single dose of SARS-CoV-2 mRNA vaccine in treated cancer patients

Author

S. Marot, Romain Palich, P. Maingon, A G Marcelin, Joseph Gligorov, Aurore Vozy, Marianne Veyri, J-P. Spano, HAL-SU, Gestionnaire, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'Oncologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Universitaire de Cancérologie [Paris] (IUC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHU Pitié-Salpêtrière], Service d'Oncologie Radiothérapie [CHU Pitié Salpétrière], Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Service de virologie [CHU Pitié-Salpêtrière]

Subjects
2019-20 coronavirus outbreak, COVID-19 Vaccines, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV.CAN]Life Sciences [q-bio]/Cancer, Serology, 03 medical and health sciences, 0302 clinical medicine, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Neoplasms, medicine, Humans, RNA, Messenger, Letter to the Editor, 030304 developmental biology, Cancer, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, Messenger RNA, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, business.industry, SARS-CoV-2, Immunogenicity, Vaccination, COVID-19, Hematology, medicine.disease, Virology, 3. Good health, mRNA vaccine, Oncology, 030220 oncology & carcinogenesis, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, business
Abstract

International audience; Active cancer and ongoing antineoplastic treatments are major factors for severe COVID-19 and death, reasons why the SARS-CoV-2 vaccination remains a priority in cancer patients (CPs). However, immunocompromised patients were excluded from major studies on mRNA vaccines, and could have a decreased response to vaccination, as recently demonstrated in solid organ transplant recipients. Herein, we aimed to assess the proportion of antibody response 4 weeks after the first injection of the BNT162b2 (Pfizer-BioNTech) vaccine in CPs and health care workers (HCWs) as the control population.

Published
2021

16. Toxicités sévères immuno-induites par les inhibiteurs de points de contrôle immunitaire : implications pour le réanimateur

Author

Anne Bachelot, Kevin Bihan, Mathieu Kerneis, Marie Bastin, Yves Allenbach, Thierry Maisonobe, Fabrizio Andreelli, Stéphane Ederhy, Jean-Philippe Spano, Aurore Vozy, Jacques Cadranel, Jean-Baptiste Bachet, A. Canellas, Sarah Leonard Louis, Joe-Elie Salem, Corinne Isnard Bagnis, Dominique Thabut, Bénédicte Lebrun Vignes, Lee S. Nguyen, Nicolas Weiss, Baptiste Hervier, Charlotte Fenioux, Dimitri Psimaras, Nicolas Bréchot, Sylvain Choquet, Céline Anquetil, and Adam Celier

Subjects
medicine.medical_specialty, business.industry, Immune checkpoint inhibitors, Cancer, Emergency Nursing, Multidisciplinary team, medicine.disease, Intensive care unit, law.invention, law, Multidisciplinary approach, Intensive care, Emergency Medicine, medicine, In patient, Intensive care medicine, business, Adverse effect
Abstract

Depuis la révolution de l’immunothérapie utilisant les inhibiteurs de points de contrôle immunitaire dans la prise en charge de nombreux cancers, les oncologues font face à de nouveaux types de toxicités dites immuno-induites. La compréhension de leurs mécanismes et la mise en place de recommandations claires sont les clés de leur prise en charge. La gravité potentielle de ces toxicités et la très nette amélioration du pronostic apportée par ces traitements pour les patients porteurs de cancers métastatiques rend le rôle du réanimateur primordial. Le but de cette mise au point est d’effectuer une synthèse des toxicités immuno-induites pouvant conduire les patients en cours de traitement par inhibiteur de points de contrôle immunitaireen réanimation et ainsi de proposer des recommandations dans leur prise en charge afin d’aider le réanimateur dans sa démarche diagnostique et thérapeutique. L’imbrication de toxicités immuno-induites pouvant toucher plusieurs organes de façon concomitante, impose une prise en charge pluridisciplinaire regroupant oncologue, spécialiste d’organes et réanimateur. La mise en place de réunion de concertation pluridisciplinaire dédiée à ce type de toxicités permet ce regroupement, de même que le développement d’une expertise commune au sein d’un centre, la création de protocoles de soins et de recherche dédiés à la compréhension et la prise en charge de ces toxicités, et ce afin d’optimiser la gestion de ces patients.

Published
2020

17. Risk factors for Coronavirus Disease 2019 (COVID-19) severity and mortality among solid cancer patients and impact of the disease on anticancer treatment: A French nationwide cohort study (GCO-002 CACOVID-19)

Author

Astrid Lièvre, Anthony Turpin, Isabelle Ray-Coquard, Karine Le Malicot, Juliette Thariat, Guido Ahle, Cindy Neuzillet, Xavier Paoletti, Olivier Bouché, Kais Aldabbagh, Pierre Michel, Didier Debieuvre, Anthony Canellas, Marie Wislez, Lucie Laurent, May Mabro, Raphael Colle, Anne-Claire Hardy-Bessard, Laura Mansi, Emeline Colomba, Jean Bourhis, Philippe Gorphe, Yoann Pointreau, Ahmed Idbaih, Renata Ursu, Anna Luisa Di Stefano, Gérard Zalcman, Thomas Aparicio, Solenne Moulin, Olivier Leleu, Sylvie Leparree, Henri Goasdoue, Christine Piprot, Gerald Tourneur, Vincent Bayart, Delphine Lignier, Emma Lachaier, Marwa Khamari, Alexandre Coutte, Nicolas Siembida, Aline Houessinon, Jean Marc Regimbeau, Bruno Chauffert, Aurélie Moreira, Vincent Hautefeuille, Christine Hee, Mathieu Boone, Céline Bihan, Emilie Chive, Stéphane Poulet-Potriquier, Rachida Fahem, Dominique Luet, Guillaume Roquin, Carole Vitellius, Nathanaëlle Cornet-Trichereau, François-Xavier Caroli-Bosc, Anne Thirot-Bidault, Stanislas Ropert, Julie Gachet - Masson, Mélanie Dehais, Gwen-Ael L'helgoualc'h, Ibrahim Ali-Mahamadou, Safia Talfi, Laure Belmont, Dieudonné Kilendo, Nasro Benrezzak, Emeline Dubief, Guillaume Conroy, Laurence Delique, Maud Basso, Isabelle Pons, Karine Salignon, Anne-Laure Villing, Emmanuelle Mougenot, Cassandra Porebski, Asma Guiatni, Nicolas Cloarec, Laurent Mineur, Marie Bouchaud, Céleste David, Annie Peytier, Thomas Greletty, Franck Audemar, Emanuelle Vignes, Floriane Minne, Guillaume Goldzak, Fabienne Huysman, Fayçal Hocine, Zaher Lakkis, Guillaume Meynard, Hamadi Almotlak, Elodie Klajer, Xu-Shan Sun, Julie Wasselin, Pascale Catala, Claire Mazuy, Hélène Vandamme, Jean-Briac Prevost, Aurélie Fadin, Laurent Basson, Jean-Baptiste Huguet, Emmanuelle Dos Santos, Bérangère Jany, Alain Saad, Frédéric Goutorbe, Eric Oziol, Mohamed Ramdani, Ouafae Kadiri, Delphine Garbay, Clotilde Huet, Etienne Giroux Leprieur, Wen Teng, Justine Monvoisin, Patrick Arnaud Coffin, Sylvie Roux, Hubert Orfeuvre, Mélanie Chagros, Didier Pillon, Agathe Rassoul, Pierre Guillaume Poureau, Cécile Novello, François Ducray, Cécile Trouba, Vianney Bastit, Emmanuel Babin, Vincent Leon, Anne-Catherine Courtecuisse, Julie Vambre, Vincent Tack, Christophe Desauw, Fatima Meniai, Christina Peres, Aurélie Esparcieux, Hervé Perrier, Nathalie Doux, Régis Kaphan, Bertrand Roques, Christine Rebischung, Dominique Mille, Gaëlle Fernandes, Naceur Abdelli, Natacha Jousset, Pierre Combe, Eric Jonveaux, Patrick Dumont, Marc Kanaan, Corinne Berthelot Gras, Valérie Panis, Laure Kaluzinski, Marjolène Venant-Valery, You-Heng Lam, Laura Vallee, Frédéric Riviere, Muriel Durand, Dihya Benghadid, Emilie Villeneuve, Olivia Hentic Dhome, Zedjiga Bounouar, Louis De Mestier, Jacqueline Dubois, Magali Eyriey, Lionel Moreau, Dib Baihas, Kaïs Aldabbagh, Dominique Degriffolet, Virginie Sebbagh, Jean-Christophe Seghezzi, Marion Lozach-Brugirard, Julie Mandrou, Loubna Mavier, Florence Hennetier, Jean-Philippe Wagner, Elisabeth Carola, Karthiga Chandirakumaran, Sandrine Loutski, Isabelle Cojean-Zelek, Amina Bouras, Sandrine Lacour, Fahem Froura, Hadjer Ben Nadji, Sophie Cattelain, Franck Darloy, Geneviève Jolimoy Boilleau, Cyrielle Maissiat, Ariane Darut-Jouve, Véronique Lorgis, Ikram Charifi-Alaoui, François Ghiringhelli, Antoine Drouillard, Marie Chaix, Sylvain Manfredi, Côme Lepage, Alice Gagnaire, Marianne Latournerie, Sofia jourdan, Nora Perrot, Mireille folia, Anne Minello, Jean-Louis Jouve, Marielle Fery, Alain Landau, Diane Evrard, Bruno Valenza, Jean-François Paitel, Laetitia Chablais, Thomas Kreitmann, Laurence Lancry-Lecomte, Adrien Monard, Eve Faugeras, Paul Boucheret, Cécile Glommeau, Christine Tchikladze, Claire Garnier Tixidre, Jérôme Long, Manel Zaidi, Véronique Delabarre, Juliette Meyzenc, Loïc Ferrand, Denis Moro-Sibilot, Paul Bouheret, Cécile Leyronnas, Camille Herve, Audrey Thoor, Emanuelle Jacquet, Gaël Roth, Videsheka Madapathage-Senanyake, Peggy Chupeau, Elsa Bieber, Maud Rosso, Isabelle Lepage, Frank Priou, Margot Laly, Sylvie Aprelon, Natacha Sobolak, Helen Homokos, Fabienne Watelle, Alice Pham-Becker, Géraldine Lauridant, Charlotte Dujardin, Etienne Lenglin, Aimée Nienguet Tsota, Sophie Dominguez, Alexandra Forestier, Franck Nouvel, Justine Lerooy, Céline Ratajczak, Olivier Romano, Dorothéee Brzyski, Aurélien Barriere, Dominique Genet, Julien Tisse, Xavier Zasadny, Adeline Grelet, Amélie Hennion-Imbault, Eglantine Haustraete, Samy Louafi, Manal Awad, Younes Zekri, Caroline Cheneau, Nolwen Leissen, Joëlle Egreteau, Alexandra Breant, Matthieu Sarabi, Stéphanie Labonne, Julien Forestier, Céline Leclercq, Florence Prunier-Bossion, Isabelle Ray Coquard, Marielle Guillet, Aurélie Theillaumas, Emilie Prome, Thomas Walter, Pierre Philouze, Melody Lawo, Solène De Talhouet, Johanne Beuvelot, Yann Molin, Marie Bellecoste Martin, Maud Saussereau, Lauren Agnelli, Nicolas Fakhry, Christophe Laplace, Emmanuelle Norguet Monnereau, Céline Boucard, Kahina Djenad, Catherine Fontaine, Jean-François Seitz, Laétitia Dahan, Julie Sigrand, Muriel Duluc, Christophe Locher, Marjory Fleury, Ange Brou Marie, Ramdane Berkane, Séverine Poupblanc, Dominique Auby, Daniela Petran, Patrick Texereau, Elodie Guerineau, Morgan Andre, Linda Mahjoubi, Fanny Sarrazin, Sonia Jeanson, Anthony Gschwend, Virginie Birr, Mathieu Fore, Monique Noirclerc, Sihem Dahou, Dominique Spaeth, Mélanie Lambotin, Thomas Lelu, Benjamin Linot, Nathalie Hugon, Dominique Rousseau, Hélène Castanie, Carole Lenne, Alain Lortholary, Anatole Cessot, Messaouda Merzoug, Cécile Naudin, Jean-Michel Vannetzel, Ghina Aziz, Yacine Hadj Arab, Stéphanie Pernes, Isabelle Roche-Lachaise, Frédéric Fiteni, Hadjer Yahiaoui, Gwendoline Marel Lopez, Jeanne Oddoz, Fabienne Peira, Olivier Michel, Jérôme Meunier, Brahim Ouahrani, Antoine Roger, Sonia Branco, Van Nguyen, Mathilde Gisselbrecht, Ghania Hammad, Pierre Mordant, Magda Stroksztejn, Marc Pocard, Luc Nlo Meyengue, Emmanuelle Sacco, Sophie Simon Anne, Elizabeth Fabre-Guillevin, Marine Slim, Aziz Zaanan, Jacques Cadranel, Johan Pluvy, Rénata Ursu, Amyrath Geraldo, Rime Lihi, Maryline Vo, Zohra Brouk, Raphaël Colle, Mostefa Bennamoun, Fabrice Lacan, Christophe Louvet, Soraya Mebarki, Marianne Veyri, Elena Paillaud, Christelle Lucas, Olivier Dubreuil, Jamila Lyamani, Hanane Agguini, Emilie Soularue, Clément Jourdaine, Benjamin Verillaud, Hakima Herzine, Eric Raymond, Nathalie Mathiot, Lola Jade Palmieri, Christian Epanya, Julien Taieb, Eliane Bertrand, Gaël Goujon, Céline Namour, Benoit Gazeau, Biljana Zafirova, Haitham Mirghani, Catherine Belin, Kahina Belkhir, Myriam Gharib, Aurore Vozy, Karim Amrane, Jean-Philippe Spano, Johanna Wassermann, Loic Feuvret, Jean-Baptiste Bachet, Sara Philonenko, Laetitia Guillot, Marion Zabbe, Stéphanie Gibiat, Camille Baylot, Aude Jouinot, Nicolas Leduc, Sabine Vieillot, Laurie James, Camille Ducerf, Jean-Frédéric Blanc, Claire Falandry Leger, Virginie Wautot, Marion Chauvenet, Aude Vincent, David Tougeron, Sandrine Goulvent, Etienne Suc, Anne-Pascale Laurenty, Eric Marquis, Margaux Bonnaire, Maxime Dewolf, Esteban Brenet, Delphine Billard, Claude-Fabien Litre, Antoine Dumazet, Damien Botsen, Marion Vazel, Claire Carlier, David Bonnerave, Charles Marchand-Crety, Olivier Bouche, Patricia Fosse, David Sefrioui, Sarah Watson, Fatah Torche, Thierry Muron, Stéphane Natur, Romain Desgrippes, Véronique Bihel, François-Régis Ferrand, Caroline Leiterer, Julie Lavole, Claire Moquet, Nathalie Pressoir, Catherine Dziukala, Catherine Ligeza Poisson, Abdelhalim Naji, Nicolas Williet, Jean-Marc Phelip, Fabrice Di Palma, Amina Kherrour Mehdi, Julien Langrand-Escure, Pierre Fournel, Grégoire Pigne, Léa Saban-Roche, Nicolas Magne, Cécile Vassal, Jean-Philippe Jacquin, Carole Ramirez, Alexis Vallard, Olivier Collard, Romain Rivoirard, Ivan Graber, Stéphanie Trager Maury, Elodie Duboisset, Jorge Ayllon Ugarte, Dalilia Rami, Christine Saler, Manon Reinbolt, Clara Le Fevre, Meher Ben Abdelghani, Louis-Marie Dourthe, Joffrey Perruisseau-Carrier, Marlène Nguimpi-Tambou, Flavie Barret, Luisa Di Stefano Anna, Annie Balthazard, Camille Vassord-Dang, Mathilde Le Marchand, Julien Vergniol, Iulia Pripon, Axelle Daemaegdt, Vanessa Latry, Muna Larrieu, Gaëlle Landry, Laetitia Touihri Maximin, Francesco Del Piano, Agnès Barlet, Mylène Vernisse, Sophie Lafond, Charline Genin, Camille Sibertin-Blanc, Emilien Chabrillac, Caroline Gregoire, Sébastien Vergez, Quentin Panouille, Rosine Guimbaud, Floriane Richa, Loïc Lebellec, Sophie Gounin, Guillaume Buiret, Marine Baudin, Hervé Hamon, Anne-Claire Deshorgue, Eduardo Barrascout, Stéphanie Legrand, Morgane Houlze, Linda Cambula, Anthony Lopez, Guillaume Fouquet, Kahina Touabi, Adeline GermaIn, Benoit Godbert, Florence Voivret, Julie Perrin, Rosa Da Silva, Emilie Bernichon, GCO-002 CACOVID-19 collaborators/investigators, Moulin, S., Leleu, O., Leparree, S., Goasdoue, H., Piprot, C., Tourneur, G., Bayart, V., Lignier, D., Lachaier, E., Khamari, M., Coutte, A., Siembida, N., Houessinon, A., Regimbeau, J.M., Chauffert, B., Moreira, A., Hautefeuille, V., Hee, C., Boone, M., Bihan, C., Chive, E., Poulet-Potriquier, S., Fahem, R., Luet, D., Roquin, G., Vitellius, C., Cornet-Trichereau, N., Caroli-Bosc, F.X., Thirot-Bidault, A., Ropert, S., Gachet-Masson, J., Dehais, M., L'helgoualc'h, G.A., Ali-Mahamadou, I., Talfi, S., Belmont, L., Kilendo, D., Benrezzak, N., Dubief, E., Conroy, G., Delique, L., Basso, M., Pons, I., Salignon, K., Villing, A.L., Mougenot, E., Porebski, C., Guiatni, A., Cloarec, N., Mineur, L., Bouchaud, M., David, C., Peytier, A., Greletty, T., Audemar, F., Vignes, E., Minne, F., Goldzak, G., Huysman, F., Hocine, F., Lakkis, Z., Mansi, L., Meynard, G., Almotlak, H., Klajer, E., Sun, X.S., Wasselin, J., Catala, P., Mazuy, C., Vandamme, H., Prevost, J.B., Fadin, A., Basson, L., Huguet, J.B., Dos Santos, E., Jany, B., Saad, A., Goutorbe, F., Oziol, E., Ramdani, M., Kadiri, O., Garbay, D., Huet, C., Giroux Leprieur, E., Teng, W., Monvoisin, J., Arnaud Coffin, P., Roux, S., Orfeuvre, H., Chagros, M., Pillon, D., Rassoul, A., Poureau, P.G., Novello, C., Ducray, F., Trouba, C., Bastit, V., Babin, E., Thariat, J., Leon, V., Courtecuisse, A.C., Vambre, J., Tack, V., Desauw, C., Meniai, F., Peres, C., Esparcieux, A., Perrier, H., Doux, N., Kaphan, R., Roques, B., Rebischung, C., Mille, D., Fernandes, G., Abdelli, N., Jousset, N., Combe, P., Jonveaux, E., Dumont, P., Kanaan, M., Berthelot Gras, C., Panis, V., Kaluzinski, L., Venant-Valery, M., Lam, Y.H., Vallee, L., Riviere, F., Durand, M., Benghadid, D., Villeneuve, E., Hentic Dhome, O., Laurent, L., Bounouar, Z., De Mestier, L., Dubois, J., Eyriey, M., Moreau, L., Ahle, G., Baihas, D., Aldabbagh, K., Degriffolet, D., Sebbagh, V., Seghezzi, J.C., Lozach-Brugirard, M., Mandrou, J., Mavier, L., Hennetier, F., Wagner, J.P., Carola, E., Chandirakumaran, K., Loutski, S., Cojean-Zelek, I., Bouras, A., Lacour, S., Froura, F., Ben Nadji, H., Cattelain, S., Darloy, F., Jolimoy Boilleau, G., Maissiat, C., Darut-Jouve, A., Lorgis, V., Charifi-Alaoui, I., Ghiringhelli, F., Drouillard, A., Chaix, M., Manfredi, S., Lepage, C., Gagnaire, A., Latournerie, M., Jourdan, S., Perrot, N., Folia, M., Minello, A., Jouve, J.L., Fery, M., Landau, A., Evrard, D., Valenza, B., Paitel, J.F., Chablais, L., Kreitmann, T., Lancry-Lecomte, L., Monard, A., Faugeras, E., Boucheret, P., Glommeau, C., Tchikladze, C., Garnier Tixidre, C., Long, J., Zaidi, M., Delabarre, V., Meyzenc, J., Ferrand, L., Moro-Sibilot, D., Bouheret, P., Leyronnas, C., Herve, C., Thoor, A., Jacquet, E., Roth, G., Madapathage-Senanyake, V., Chupeau, P., Bieber, E., Rosso, M., Lepage, I., Priou, F., Laly, M., Aprelon, S., Sobolak, N., Homokos, H., Pointreau, Y., Watelle, F., Pham-Becker, A., Lauridant, G., Turpin, A., Dujardin, C., Lenglin, E., Nienguet Tsota, A., Dominguez, S., Forestier, A., Nouvel, F., Lerooy, J., Ratajczak, C., Romano, O., Brzyski, D., Barriere, A., Genet, D., Tisse, J., Zasadny, X., Grelet, A., Hennion-Imbault, A., Haustraete, E., Louafi, S., Awad, M., Zekri, Y., Cheneau, C., Leissen, N., Egreteau, J., Breant, A., Sarabi, M., Labonne, S., Forestier, J., Leclercq, C., Prunier-Bossion, F., Ray Coquard, I., Guillet, M., Theillaumas, A., Prome, E., Walter, T., Philouze, P., Lawo, M., De Talhouet, S., Beuvelot, J., Molin, Y., Bellecoste Martin, M., Saussereau, M., Agnelli, L., Fakhry, N., Laplace, C., Norguet Monnereau, E., Boucard, C., Djenad, K., Fontaine, C., Seitz, J.F., Dahan, L., Sigrand, J., Duluc, M., Locher, C., Fleury, M., Brou Marie, A., Berkane, R., Poupblanc, S., Auby, D., Petran, D., Texereau, P., Guerineau, E., Andre, M., Mahjoubi, L., Sarrazin, F., Jeanson, S., Gschwend, A., Birr, V., Debieuvre, D., Fore, M., Noirclerc, M., Dahou, S., Spaeth, D., Lambotin, M., Lelu, T., Linot, B., Hugon, N., Rousseau, D., Castanie, H., Lenne, C., Lortholary, A., Cessot, A., Merzoug, M., Naudin, C., Vannetzel, J.M., Aziz, G., Hadj Arab, Y., Pernes, S., Roche-Lachaise, I., Fiteni, F., Yahiaoui, H., Marel Lopez, G., Oddoz, J., Peira, F., Michel, O., Meunier, J., Ouahrani, B., Roger, A., Branco, S., Nguyen, V., Gisselbrecht, M., Hammad, G., Mordant, P., Stroksztejn, M., Pocard, M., Nlo Meyengue, L., Aparicio, T., Sacco, E., Simon Anne, S., Fabre-Guillevin, E., Wislez, M., Slim, M., Zaanan, A., Cadranel, J., Pluvy, J., Ursu, R., Geraldo, A., Lihi, R., Vo, M., Brouk, Z., Colle, R., Bennamoun, M., Lacan, F., Louvet, C., Mebarki, S., Veyri, M., Paillaud, E., Lucas, C., Dubreuil, O., Lyamani, J., Idbaih, A., Agguini, H., Soularue, E., Canellas, A., Zalcman, G., Jourdaine, C., Verillaud, B., Herzine, H., Raymond, E., Mathiot, N., Palmieri, L.J., Epanya, C., Taieb, J., Bertrand, E., Goujon, G., Namour, C., Gazeau, B., Zafirova, B., Mirghani, H., Belin, C., Belkhir, K., Gharib, M., Vozy, A., Amrane, K., Spano, J.P., Wassermann, J., Feuvret, L., Bachet, J.B., Philonenko, S., Guillot, L., Zabbe, M., Gibiat, S., Baylot, C., Jouinot, A., Leduc, N., Vieillot, S., James, L., Ducerf, C., Blanc, J.F., Falandry Leger, C., Wautot, V., Chauvenet, M., Vincent, A., Tougeron, D., Goulvent, S., Suc, E., Laurenty, A.P., Marquis, E., Bonnaire, M., Dewolf, M., Brenet, E., Billard, D., Litre, C.F., Dumazet, A., Botsen, D., Vazel, M., Carlier, C., Bonnerave, D., Marchand-Crety, C., Bouche, O., Fosse, P., Sefrioui, D., Michel, P., Watson, S., Neuzillet, C., Torche, F., Muron, T., Natur, S., Desgrippes, R., Bihel, V., Ferrand, F.R., Leiterer, C., Lavole, J., Moquet, C., Pressoir, N., Dziukala, C., Ligeza Poisson, C., Naji, A., Williet, N., Phelip, J.M., Di Palma, F., Kherrour Mehdi, A., Langrand-Escure, J., Fournel, P., Pigne, G., Saban-Roche, L., Magne, N., Vassal, C., Jacquin, J.P., Ramirez, C., Vallard, A., Collard, O., Rivoirard, R., Graber, I., Trager Maury, S., Duboisset, E., Ayllon Ugarte, J., Rami, D., Saler, C., Reinbolt, M., Le Fevre, C., Ben Abdelghani, M., Dourthe, L.M., Perruisseau-Carrier, J., Nguimpi-Tambou, M., Barret, F., Di Stefano Anna, L., Balthazard, A., Mabro, M., Vassord-Dang, C., Le Marchand, M., Vergniol, J., Pripon, I., Daemaegdt, A., Latry, V., Larrieu, M., Landry, G., Touihri Maximin, L., Del Piano, F., Barlet, A., Vernisse, M., Lafond, S., Genin, C., Sibertin-Blanc, C., Chabrillac, E., Gregoire, C., Vergez, S., Panouille, Q., Guimbaud, R., Richa, F., Lebellec, L., Gounin, S., Buiret, G., Baudin, M., Hamon, H., Deshorgue, A.C., Barrascout, E., Legrand, S., Houlze, M., Cambula, L., Lopez, A., Fouquet, G., Touabi, K., GermaIn, A., Godbert, B., Voivret, F., Perrin, J., Da Silva, R., Bernichon, E., Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), CH Colmar, Institut Curie [Paris], Centre Hospitalier Universitaire de Reims (CHU Reims), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Beaujon, Hôpital Foch [Suresnes], CHU Saint-Antoine [AP-HP], ARCAGY-GINECO, 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), Institut Gustave Roussy (IGR), Département de médecine nucléaire [Rennes], CRLCC Eugène Marquis (CRLCC), Département de médecine oncologique [Gustave Roussy], Département de cancérologie cervico-faciale [Gustave Roussy] (CCF), Centre Jean Bernard [Institut Inter-régional de Cancérologie - Le Mans], Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hopital Saint-Louis [AP-HP] (AP-HP), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), AbbVie, Merck, Carthera, Transgene, Nutritheragene, Roche, Air Liquide, Eli Lilly Japan, LEO Pharma Research Foundation, Bayer, Novartis, Sanofi, Biogen, Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, 0301 basic medicine, Cancer Research, medicine.medical_treatment, Disease, law.invention, Cohort Studies, 0302 clinical medicine, Mechanical ventilation, Risk Factors, law, Neoplasms, Medicine, Prospective Studies, Prospective cohort study, Original Research, Cancer, Intensive care unit, 3. Good health, Death, Oncology, 030220 oncology & carcinogenesis, Female, France, Immunotherapy, Cohort study, medicine.medical_specialty, chemotherapy. radiotherapy, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Internal medicine, Humans, Chemotherapy, Mortality, Pandemics, Aged, Retrospective Studies, Radiotherapy, SARS-CoV-2, business.industry, COVID-19, Retrospective cohort study, Odds ratio, medicine.disease, Antineoplastic Agents/adverse effects, Antineoplastic Agents/therapeutic use, COVID-19/mortality, France/epidemiology, Neoplasms/mortality, Neoplasms/therapy, Neoplasms/virology, SARS-CoV-2/isolation & purification, 030104 developmental biology, business
Abstract

Background Cancer patients are thought to have an increased risk of developing severe Coronavirus Disease 2019 (COVID-19) infection and of dying from the disease. In this work, predictive factors for COVID-19 severity and mortality in cancer patients were investigated. Patients and Methods In this large nationwide retro-prospective cohort study, we collected data on patients with solid tumours and COVID-19 diagnosed between March 1 and June 11, 2020. The primary endpoint was all-cause mortality and COVID-19 severity, defined as admission to an intensive care unit (ICU) and/or mechanical ventilation and/or death, was one of the secondary endpoints. Results From April 4 to June 11, 2020, 1289 patients were analysed. The most frequent cancers were digestive and thoracic. Altogether, 424 (33%) patients had a severe form of COVID-19 and 370 (29%) patients died. In multivariate analysis, independent factors associated with death were male sex (odds ratio 1.73, 95%CI: 1.18-2.52), ECOG PS ≥ 2 (OR 3.23, 95%CI: 2.27-4.61), updated Charlson comorbidity index (OR 1.08, 95%CI: 1.01-1.16) and admission to ICU (OR 3.62, 95%CI 2.14-6.11). The same factors, age along with corticosteroids before COVID-19 diagnosis, and thoracic primary tumour site were independently associated with COVID-19 severity. None of the anticancer treatments administered within the previous 3 months had any effect on mortality or COVID-19 severity, except cytotoxic chemotherapy in the subgroup of patients with detectable SARS-CoV-2 by RT-PCR, which was associated with a slight increase of the risk of death (OR 1.53; 95%CI: 1.00-2.34; p = 0.05). A total of 431 (39%) patients had their systemic anticancer treatment interrupted or stopped following diagnosis of COVID-19. Conclusions Mortality and COVID-19 severity in cancer patients are high and are associated with general characteristics of patients. We found no deleterious effects of recent anticancer treatments, except for cytotoxic chemotherapy in the RT-PCR-confirmed subgroup of patients. In almost 40% of patients, the systemic anticancer therapy was interrupted or stopped after COVID-19 diagnosis., Highlights • A total of 1289 patients with solid tumours and COVID-19 were analysed. • Mortality and COVID-19 severity were mainly driven by patient general characteristics. • Overall, we found no deleterious effects of recent anticancer treatments on mortality. . • Systemic anticancer treatment was interrupted or stopped in 39% of patients.

Published
2020

18. Clinical Pharmacology and Interplay of Immune Checkpoint Agents: A Yin-Yang Balance

Author

Joe-Elie Salem, Aurore Vozy, Paul Gougis, Javid Moslehi, Yves Allenbach, Elisa Funck-Brentano, Douglas B. Johnson, Arthur Geraud, Emanuela Romano, Céline Anquetil, Service de pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Institut Gustave Roussy (IGR), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Ambroise Paré [AP-HP], Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
0301 basic medicine, T cell, [SDV]Life Sciences [q-bio], Cell, chemical and pharmacologic phenomena, Toxicology, law.invention, Autoimmune Diseases, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antineoplastic Agents, Immunological, Downregulation and upregulation, law, Neoplasms, Medicine, Cytotoxic T cell, Humans, Yin-Yang, Pharmacology, Clinical pharmacology, business.industry, Cancer, medicine.disease, Immune checkpoint, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Immunology, Immunotherapy, business
Abstract

International audience; T cells have a central role in immune system balance. When activated, they may lead to autoimmune diseases. When too anergic, they contribute to infection spread and cancer proliferation. Immune checkpoint proteins regulate T cell function, including cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) and its ligand (PD-L1). These nodes of self-tolerance may be exploited pharmacologically to downregulate (CTLA-4 agonists) and activate [CTLA-4 and PD-1/PD-L1 antagonists, also called immune checkpoint inhibitors (ICIs)] the immune system. CTLA-4 agonists are used to treat rheumatologic immune disorders and graft rejection. CTLA-4, PD-1, and PD-L1 antagonists are approved for multiple cancer types and are being investigated for chronic viral infections. Notably, ICIs may be associated with immune-related adverse events (irAEs), which can be highly morbid or fatal. CTLA-4 agonism has been a promising method to reverse such life-threatening irAEs. Herein, we review the clinical pharmacology of these immune checkpoint agents with a focus on their interplay in human diseases. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 61 is January 8, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Published
2020

19. Systemic short chain fatty acids limit antitumor effect of CTLA-4 blockade in hosts with cancer

Author

Julien Schmidt, Ludovic Lacroix, Atmane Seck, Aurore Vozy, Patrick Saulnier, Jonathan Grivel, Nathalie Chaput, Jean Mehdi Jouniaux, Ester Simeone, Franck Carbonnel, Paolo A. Ascierto, Laetitia Nebot-Bral, M. Naigeon, Domenico Mallardo, L. Boselli, Paul Louis Woerther, Caroline Robert, Lydie Cassard, Patricia Lepage, Angelo Paci, Clélia Coutzac, Mélanie Desbois, Christine Mateus, V. Asvatourian, Emilie Soularue, Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France, Laboratoire d’Immunomonitoring en Oncologie (LIO), Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Faculté de Médecine Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Université Paris-Saclay, Institut Gustave Roussy (IGR), Vectorologie et thérapeutiques anti-cancéreuses [Villejuif] (UMR 8203), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay, Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], 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, IRCCS Istituto Nazionale dei Tumori [Milano], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Instituto Nazionale Tumori-Fondazione 'G. Pascale', Direction de la recherche [Gustave Roussy], Fondation Gustave Roussy Direction Générale de l’offre de Soins, DGOS: TRANSLA 12-174 Institut National de la Santé et de la Recherche Médicale, Inserm Centre National de la Recherche Scientifique, CNRS: INCa-DGOS-INSERM_12551, ANR-10IBHU-0001 Fondation Gustave Roussy Institut National Du Cancer, INCa: 2012-1-RT-14-IGR-01 Fondation pour la Recherche Médicale, FRM AstraZeneca Sanofi GlaxoSmithKline Australia, GSK, The authors thank Dr. Patrick Gonin from the PlatForm for Preclinical Evaluation (PFEP). Fundings: This study was funded by Gustave Roussy Cancer Campus, Fondation Gustave Roussy, the Institut national de la santé et de la recherche médicale (INSERM), the Centre national de la recherche scientifique (CNRS), SIRIC SOCRATE (INCa DGOS INSERM 6043), SIRIC SOCRATE 2.0 (INCa-DGOS-INSERM_12551), MMO program: ANR-10IBHU-0001), Direction General de l’Offre de Soins (DGOS, TRANSLA 12-174), Institut National du Cancer (INCa, 2012-062 N_ Canceropole: 2012-1-RT-14-IGR-01). Dr. Clélia Coutzac was supported by fellowships from Fondation pour la Recherche Medicale (FRM) from 2015 to 2016., N.C. reports research grants from Cytune Pharma, GSK, Sanofi, has participated in advisory boards for AstraZeneca and has been a speaker for Sanofi and AstraZeneca. C.R. has participated in advisory boards for Roche, GSK, Merck, Novartis, Amgen, BMS and Novartis. Franck Carbonnel received boards or lecture fees from enterome, Amgen, Astra, MSD, BMS, Janssen, Pfizer, Abbvie, Mayoly Spindler, Takeda, Pileje, Roche. E. Soularue has participated in advisory board for Novartis. L.L. has participated in advisory boards for Roche, Astrazeneca, BMS, Genomic Health, Illumina, Qiagen, Novartis Thermofisher and has been a speaker for Amgen, AstraZeneca, Dyn, Vela diagnostics, Luye Pharma, and Roche. P.A.A. has/had a consultant/advisory role for Bristol Myers-Squibb, Roche-Genentech, Merck Sharp & Dohme, Array, Novartis, Amgen, Merck Serono, Pierre Fabre, Incyte, NewLink Genetics, Genmab, Medimmune, AstraZeneca, Syndax, SunPharma, Sanofi, Idera. He also received Research funds from Bristol Myers-Squibb, Roche-Genentech, Array. The other authors have no conflicts of interest to declare., and ANR-10-IBHU-0001,MMO (IHU-CANCER),Institut de Médecine Personnalisée du Cancer(2010)

Subjects
0301 basic medicine, [SDV]Life Sciences [q-bio], T-Lymphocytes, medicine.medical_treatment, General Physics and Astronomy, Pharmacology, Gut flora, T-Lymphocytes, Regulatory, Immune tolerance, Tumour biomarkers, Mice, 0302 clinical medicine, Neoplasms, RNA, Ribosomal, 16S, CTLA-4 Antigen, lcsh:Science, Cancer, Mice, Inbred BALB C, Multidisciplinary, biology, Chemistry, hemic and immune systems, 3. Good health, Butyrates, 030220 oncology & carcinogenesis, B7-1 Antigen, Science, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, chemical and pharmacologic phenomena, Butyrate, digestive system, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Immune system, Biomarkers, Tumor, medicine, Animals, Humans, CD86, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Dendritic Cells, General Chemistry, Immunotherapy, Fatty Acids, Volatile, biology.organism_classification, Ipilimumab, Gastrointestinal Microbiome, 030104 developmental biology, CTLA-4, lcsh:Q, B7-2 Antigen, Propionates, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Biomarkers, CD80
Abstract

Gut microbiota composition influences the clinical benefit of immune checkpoints in patients with advanced cancer but mechanisms underlying this relationship remain unclear. Molecular mechanism whereby gut microbiota influences immune responses is mainly assigned to gut microbial metabolites. Short-chain fatty acids (SCFA) are produced in large amounts in the colon through bacterial fermentation of dietary fiber. We evaluate in mice and in patients treated with anti-CTLA-4 blocking mAbs whether SCFA levels is related to clinical outcome. High blood butyrate and propionate levels are associated with resistance to CTLA-4 blockade and higher proportion of Treg cells. In mice, butyrate restrains anti-CTLA-4-induced up-regulation of CD80/CD86 on dendritic cells and ICOS on T cells, accumulation of tumor-specific T cells and memory T cells. In patients, high blood butyrate levels moderate ipilimumab-induced accumulation of memory and ICOS + CD4 + T cells and IL-2 impregnation. Altogether, these results suggest that SCFA limits anti-CTLA-4 activity., The gut microbiota has been reported to regulate the efficacy of cancer therapy. Here, the authors show that short-chain fatty acids, which are generated through bacterial fermentation, increases immune tolerance leading to resistance to anti-CTLA-4 immunotherapy in mice and patients with metastatic melanoma.

Published
2020

20. Cardiotoxicity Associated with Gemcitabine: Literature Review and a Pharmacovigilance Study

Author

Javid Moslehi, Bénédicte Lebrun-Vignes, Stéphane Ederhy, Aurore Vozy, Christian Funck-Brentano, Ariel Cohen, Xavier Waintraub, Lee S. Nguyen, Marc Hilmi, Joe-Elie Salem, Gestionnaire, HAL Sorbonne Université 5, Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Cardiologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Institut de cardiologie [CHU Pitié-Salpêtrière], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Vanderbilt University School of Medicine [Nashville], Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP]

Subjects
Oncology, medicine.medical_specialty, Myocardial ischemia, cardio-oncology, MEDLINE, lcsh:Medicine, lcsh:RS1-441, Pharmaceutical Science, heart failure, 030204 cardiovascular system & hematology, pericarditis, Article, lcsh:Pharmacy and materia medica, 03 medical and health sciences, Pericarditis, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Drug Discovery, Pharmacovigilance, medicine, Cardiotoxicity, business.industry, Clinical study design, lcsh:R, gemcitabine, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, Gemcitabine, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, myocardial ischemia, 030220 oncology & carcinogenesis, Heart failure, Molecular Medicine, business, arrhythmias, medicine.drug
Abstract

Background: Gemcitabine is a nucleoside analog, widely used either alone or in combination, for the treatment of multiple cancers. However, gemcitabine may also be associated with cardiovascular adverse-drug-reactions (CV-ADR). Methods: First, we searched for all cases of cardiotoxicity associated with gemcitabine, published in MEDLINE on 30 May 2019. Then, we used VigiBase, the World Health Organization&rsquo, s global database of individual case safety reports, to compare CV-ADR reporting associated with gemcitabine against the full database between inception and 01 April 2019. We used the information component (IC), an indicator value for disproportionate Bayesian reporting. A positive lower end of the 95% credibility interval for the IC (IC025) &ge, 0, is deemed significant. Results: In VigiBase, 46,898 reports were associated with gemcitabine on a total of 18,908,940 in the full database. Gemcitabine was associated with higher reporting for myocardial ischemia (MI, n: 119), pericardial diseases (n: 164), supraventricular arrhythmias (SVA, n: 308) and heart failure (HF, n: 484) versus full database with IC025 ranging between 0.40 and 2.81. CV-ADR were associated with cardiovascular death in up to 17% of cases. Conclusion: Treatment with gemcitabine is associated with potentially lethal CV-ADRs, including MI, pericardial diseases, SVA and HF. These events should be considered in patient care and clinical trial design.

Published
2020

21. Evaluation of Readministration of Immune Checkpoint Inhibitors After Immune-Related Adverse Events in Patients With Cancer

Author

Jean-Marie Michot, Stéphane Champiat, Aurore Vozy, Aurélien Marabelle, Audrey Lallart, Christophe Massard, Anne Laure Voisin, A. Simonaggio, Olivier Lambotte, Geoffray Cengizalp, Andrea Varga, Ariane Laparra, Michael Collins, Jérôme Le Pavec, and Antoine Hollebecque

Subjects
Hepatitis, Cancer Research, medicine.medical_specialty, business.industry, Incidence (epidemiology), Cancer, medicine.disease, Gastroenterology, Clinical trial, 03 medical and health sciences, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Internal medicine, Clinical endpoint, medicine, 030212 general & internal medicine, Adverse effect, business, Pneumonitis, Cohort study, Original Investigation
Abstract

Importance Although immune checkpoint inhibitors (ICIs), such as anti–PD-1 (programmed cell death 1) or anti–PD-L1 (programmed cell death 1 ligand 1), have proved effective in treating many cancers, patients receiving ICIs may experience immune-related adverse events (irAEs). Little evidence exists on the safety of resuming these treatments after an irAE. Objective To investigate the safety of a rechallenge with anti–PD-1 or anti–PD-L1 immunotherapies after an irAE. Design, Setting, and Participants This cohort study of the safety of an ICI rechallenge involved consecutive adult patients (n = 93) who were referred to the ImmunoTOX assessment board at the Gustave Roussy cancer center in Villejuif, France, between August 1, 2015, and December 31, 2017. Data were analyzed from May 28 to November 25, 2018. Main Outcomes and Measures Incidence of a second irAE in patients who had a readministration of an anti–PD-1 or anti–PD-L1 inhibitor after an initial grade 2 or higher irAE. Characteristics of the patients and the irAEs were reviewed, and the primary end point was the rate of occurrence of second irAEs. Results A total of 93 patients were included, among whom 48 (52%) were female, and the median (range) age was 62.5 (33-85) years. The main cancer types or tumor sites were melanoma (31 [33%]), lung (15 [16%]), colorectal (8 [9%]), and lymphoma (8 [9%]). For the initial irAE, 43 grade 2 events (46%), 36 grade 3 events (39%), and 14 grade 4 events (15%) were found, presenting primarily as hepatitis (17 [18%]), skin toxic effect (14 [15%]), pneumonitis (13 [14%]), colitis (11 [12%]), or arthralgia (7 [7.5%]). Forty patients (43%) were rechallenged with the same anti–PD-1 or anti–PD-L1 agent. The rechallenged and non-rechallenged groups did not differ in terms of median (range) age (61 [34-84] years vs 63 [33-85] years;P = .37), time to initial irAE (5 [1-40] treatment cycles vs 3 [1-22] treatment cycles;P = .32), irAE severity (grade 2: 18 [47.5%] vs 27 [51%]; grades 3-4: 22 [52.5%] vs 26 [49%];P = .70), or steroid use (17 [42.5%] vs 32 [60%];P = .09). With a median follow-up period of 14 months, the same irAE or a different irAE occurred in 22 patients (55%). Shorter time to the initial irAE was linked to the occurrence of a second irAE (9 vs 15 weeks;P = .04). The second irAEs were not found to be more severe than the first. Conclusions and Relevance The risk-reward ratio for an anti–PD-1 or anti–PD-L1 rechallenge appears to be acceptable, although these patients require close monitoring; further investigation into rechallenge conditions through a prospective clinical trial is needed.

Published
2019

22. 1627MO Systemic therapies in advanced epithelioid haemangioendothelioma (EHE): A retrospective international series from the World Sarcoma Network

Author

T. Wei-Wu Chen, Shintaro Iwata, S. Lo Vullo, Aurore Vozy, Silvia Stacchiotti, Antonella Brunello, Vinod Ravi, Nicolas Penel, Giacomo Giulio Baldi, W.T.A. van der Graaf, Antoine Italiano, Francesco Tolomeo, A. Fedenko, Bruno Vincenzi, A.M. Frezza, Paweł Teterycz, Nadia Hindi, Florence Duffaud, Alannah Smrke, and Hans Gelderblom

Subjects
Epithelioid haemangioendothelioma, medicine.medical_specialty, Oncology, business.industry, medicine, Hematology, Sarcoma, medicine.disease, business, Dermatology
Published
2020

23. Abstract 2268: Agonistic T cell non depleting ICOS antibody strongly enhances anti-tumor activity with CTLA4 blocking monoclonal antibody without exacerbating colitis

Author

Clélia Coutzac, Jean Jouniaux, Aurore Vozy, Marc Ballas, Sara Brett, Sapna Yadavilli, Eric Angevin, Axel Hoos, and Nathalie Chaput

Subjects
Cancer Research, Oncology
Abstract

Background: ICOS is a member of the CD28 superfamily mainly expressed on activated T cells. An up-regulation of ICOS+ T cells is observed in patients treated with ipilimumab. These findings prompt further studies examining the synergy between CTLA-4 blockade and ICOS stimulation in generating optimal anti-tumor T cell immunity. Methods: Peripheral blood mononuclear cells (PBMC) were collected from French patients with metastatic melanoma and treated with ipilimumab at baseline (V1) and after 1-2 ipilimumab infusion and restimulated in vitro with anti-CD3 plus anti-human non-depleting agonist ICOS IgG4 isotype antibodies. T cell proliferation and cytokine secretion was determined after 24 and 48h incubation. For in vivo experiments, C57Bl/6 and BALB/c mice were inoculated subcutaneously with MC38 and CT26 tumor cell lines respectively. Mice received intraperitoneal injections of anti-CTLA4 or its isotype control along with anti-mouse ICOS or corresponding isotype at D7, D10 and D13 with tumor growth assessments three times a week. Results: PBMC collected from patients that respond to anti-CTLA-4 mAb exhibited stronger activation of T cells at baseline compared to patients with poor benefit. Treatment with a non-depleting agonist ICOS IgG4 mAb was able to rescue T cell activation in PBMC from patients with poor benefit. Furthermore, ICOS IgG4 with concurrent TCR engagement favored IL-10 secretion in patients that do not develop colitis during ipilimumab treatment suggesting that these patients may be protected from colitis due to a stronger capacity to secrete IL-10 after ipilimumab blockade particularly when ICOS is stimulated. In both mouse tumor models, combination with agonist non-depleting ICOS mAb increased the anti-CTLA-4 tumor activity without any colitis development. Conclusion: This study provides evidence in mice and in humans that non-depleting agonistic ICOS mAb may increase anti-CTLA-4 tumor activity particularly in patients that do not benefit from anti-CTLA-4 alone without exacerbation of colitis. Citation Format: Clélia Coutzac, Jean Jouniaux, Aurore Vozy, Marc Ballas, Sara Brett, Sapna Yadavilli, Eric Angevin, Axel Hoos, Nathalie Chaput. Agonistic T cell non depleting ICOS antibody strongly enhances anti-tumor activity with CTLA4 blocking monoclonal antibody without exacerbating colitis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2268.

Published
2019

24. Prognostic factors and therapeutic options for epithelioid hemangioendothelioma (EHE): A multicenter analysis of a series of fifty-seven cases

Author

Olivier Mir, Sarah Dumont, Philippe Terrier, A. Simonaggio, Charles Honoré, Nicolas Penel, Jean-Philippe Spano, Aurore Vozy, Valérie Paradis, and Axel Le Cesne

Subjects
Cancer Research, Pathology, medicine.medical_specialty, Oncology, business.industry, Mesenchymal Tumor, medicine, Disease, medicine.disease, business, Epithelioid hemangioendothelioma
Abstract

11062 Background: EHE is a rare vascular mesenchymal tumor for which there is currently no standard for treatment particularly for metastatic disease. EHE often present metastatic evolution but metastases are not a poor prognostic factor. The aim of this study was to improve knowledge of outcome of EHE patients and see the impact of active surveillance on outcome for metastatic EHE patients. Methods: Patients with EHE treated at three centers in France were included in this retrospective cohort. Univariate analysis of prognostic factors was performed using the Cox model. Survival was estimated using the Kaplan-Meier method and long rank analysis. Results: Fifty-seven patients with EHE were collected in this analysis: 27 (47%) women and 30 (53%) men, with a median age at diagnosis of 39 years (range, 12-83). At diagnosis, 17 (29.8%) patients had a localized tumor, while 40 (70.2%) patients had synchronous metastases. The most commonly affected organs were liver (29.8%), bones (14.0%), skin, lungs and soft tissues (10.5% each). For the 17 patients with localized EHE, the median distant recurrence-free survival after resection of primary was 64.6 months, 95% CI [29.4, NA], (median follow-up of 62.7 months, range, 12.5-234.8). For the 40 patients with metastatic EHE, the median progression-free survival (PFS) was 59.0 months, 95% CI [21.3, NA], (median follow-up of 121.1 months, range, 1.0-202.0). No prognostic factor was identified for localized EHE. For metastatic EHE, age was associated with progression (p = 0.019), and presence of pleural/ascites/pericarditis effusion adversely affected overall survival (OS) (p = 0.002). An initial “wait and see” attitude was proposed to 23 patients (57.5%) while 17 patients (42.5%) were treated at diagnosis with local or systemic treatment (monotherapy or combination of chemotherapy with anthracyclin, taxane, cyclophosphamide). OS were similar in both groups of patients, 174months and 121months for chemotherapy treated patients and active surveillance patients respectively (p = 0.56). Conclusions: Presence of effusion was a significant poor prognostic factor in metastatic EHE patients. Active surveillance could be proposed for asymptomatic patients without effusion but this strategy need to be confirmed in largest or prospective randomized trials.

Published
2019

25. Inclusion of adolescents in adult early phase trials and young adults in paediatric early phase trials: A reality or a myth?

Author

Birgit Geoerger, P. Berlanga Charriel, Christophe Massard, Nathalie Gaspar, and Aurore Vozy

Subjects
Gerontology, 03 medical and health sciences, 0302 clinical medicine, Oncology, business.industry, 030220 oncology & carcinogenesis, Medicine, 030212 general & internal medicine, Hematology, Young adult, business, Early phase, Inclusion (education)
Published
2018

27. Applicability of the lung immune prognostic index (LIPI) to metastatic triple negative breast cancer (mTNBC) patients treated with immune checkpoint targeted monoclonal antibodies (ICT mAbs)

Author

Capucine Baldini, Benjamin Besse, Vincent Ribrag, Andreea Varga, Stéphane Champiat, Edouard Auclin, Jean-Charles Soria, Ratislav Bahleda, Sophie Postel-Vinay, Suzette Delaloge, Patricia Martin-Romano, A. Simonaggio, Laura Mezquita, Christophe Massard, A. Gazzah, Aurore Vozy, Fabrice Andre, and Barbara Pistilli

Subjects
Lung, business.industry, medicine.drug_class, Hematology, Monoclonal antibody, Immune checkpoint, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Immune system, Oncology, 030220 oncology & carcinogenesis, Cancer research, Medicine, business, Triple-negative breast cancer
Published
2018

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