91 results on '"Marina Motta"'
Search Results
2. P646: VENETOCLAX RETREATMENT AFTER MRD-GUIDED VENETOCLAX +/- IBRUTINIB: THE IMPROVE STUDY COHORT
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Lydia Scarfò, Silvia Heltai, Elisa Albi, Eloise Scarano, Luana Schiattone, Lucia Farina, Riccardo Moia, Marina Deodato, Andrea Ferrario, Marina Motta, Alessandro Noto, Rosaria Sancetta, Marta Coscia, Paolo Rivela, Luca Laurenti, Marzia Varettoni, Eleonora Perotta, Antonella Capasso, Pamela Ranghetti, Francesca Martini, Emanuela Sant’antonio, Catalina Combi, Maria Colia, and Paolo Ghia
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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3. Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19: a study of ERIC, the European Research Initiative on CLL
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Darko Antic, Natasa Milic, Thomas Chatzikonstantinou, Lydia Scarfò, Vladimir Otasevic, Nina Rajovic, David Allsup, Alejandro Alonso Cabrero, Martin Andres, Monica Baile Gonzales, Antonella Capasso, Rosa Collado, Raul Cordoba, Carolina Cuéllar-García, Juan Gonzalo Correa, Lorenzo De Paoli, Maria Rosaria De Paolis, Giovanni Del Poeta, Maria Dimou, Michael Doubek, Maria Efstathopoulou, Shaimaa El-Ashwah, Alicia Enrico, Blanca Espinet, Lucia Farina, Angela Ferrari, Myriam Foglietta, Alberto Lopez-Garcia, José A. García-Marco, Rocío García-Serra, Massimo Gentile, Eva Gimeno, Maria Gomes da Silva, Odit Gutwein, Yervand K. Hakobyan, Yair Herishanu, José Ángel Hernández-Rivas, Tobias Herold, Gilad Itchaki, Ozren Jaksic, Ann Janssens, Olga B. Kalashnikova, Elżbieta Kalicińska, Arnon P. Kater, Sabina Kersting, Maya Koren-Michowitz, Jorge Labrador, Deepesh Lad, Luca Laurenti, Alberto Fresa, Mark-David Levin, Carlota Mayor Bastida, Lara Malerba, Roberto Marasca, Monia Marchetti, Juan Marquet, Biljana Mihaljevic, Ivana Milosevic, Fatima Mirás, Marta Morawska, Marina Motta, Talha Munir, Roberta Murru, Raquel Nunes, Jacopo Olivieri, Miguel Arturo Pavlovsky, Inga Piskunova, Viola Maria Popov, Francesca Maria Quaglia, Giulia Quaresmini, Gianluigi Reda, Gian Matteo Rigolin, Amit Shrestha, Martin Šimkovič, Svetlana Smirnova, Martin Špaček, Paolo Sportoletti, Oana Stanca, Niki Stavroyianni, Doreen Te Raa, Kristina Tomic, Sanne Tonino, Livio Trentin, Ellen Van Der Spek, Michel van Gelder, Marzia Varettoni, Andrea Visentin, Candida Vitale, Vojin Vukovic, Ewa Wasik-Szczepanek, Tomasz Wróbel, Lucrecia Yáñez San Segundo, Mohamed Yassin, Marta Coscia, Alessandro Rambaldi, Emili Montserrat, Robin Foà, Antonio Cuneo, Marc Carrier, Paolo Ghia, and Kostas Stamatopoulos
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CLL ,COVID-19 ,Thrombosis ,Bleeding ,D-dimer ,Anticoagulation therapy ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. Methods This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. Results A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR = 1.022, 95%CI 1.007‒1.038 and OR = 1.025, 95%CI 1.001‒1.051, respectively), while thromboprophylaxis use was protective (OR = 0.199, 95%CI 0.061‒0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR = 1.062, 95%CI 1.017–1.109 and OR = 2.438, 95%CI 1.023–5.813, respectively). Conclusions Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.
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- 2022
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4. Long-term follow-up of cladribine treatment in hairy cell leukemia: 30-year experience in a multicentric Italian study
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Livio Pagano, Marianna Criscuolo, Alessandro Broccoli, Alfonso Piciocchi, Marzia Varettoni, Eugenio Galli, Antonella Anastasia, Maria Cantonetti, Livio Trentin, Sofia Kovalchuk, Lorella Orsucci, Annamaria Frustaci, Angelica Spolzino, Stefano Volpetti, Ombretta Annibali, Sergio Storti, Caterina Stelitano, Francesco Marchesi, Massimo Offidani, Beatrice Casadei, Maria Elena Nizzoli, Maria Lucia De Luca, Luana Fianchi, Marina Motta, Luca Guarnera, Edoardo Simonetti, Andrea Visentin, Francesco Vassallo, Marina Deodato, Chiara Sarlo, Attilio Olivieri, Brunangelo Falini, Alessandro Pulsoni, Enrico Tiacci, and Pier Luigi Zinzani
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Hairy cell leukemia (HCL) is a rare lymphoproliferative disease with an excellent prognosis after treatment with cladribine (2CDA), although relapse may occur during follow-up. The aim of the study is to review the efficacy, safety, long-term remission rate, and overall survival (OS) in those patients who received 2CDA as first-line treatment. We retrospectively reviewed data of HCL patients treated with 2CDA between March 1991 and May 2019 at 18 Italian Hematological centers: 513 patients were evaluable for study purpose. The median age was 54 years (range 24–88) and ECOG was 0 in 84.9% of cases. A total of 330 (64.3%) patients received 2CDA intravenously and 183 (35.7%) subcutaneously. ORR was 91.8%: CR was obtained in 335 patients (65.3%), PR in 96 (18.7%), and hematological response in 40 (7.8%) patients; in 42 (8.2%) no response was observed. Hemoglobin value (p = 0.044), frequency of circulating hairy cells (p = 0.039), recovery of absolute neutrophil count (p = 0.006), and normalization of spleen (p ≤ 0.001) were associated with CR compared to PR in univariable analysis. At a median follow-up of 6.83 years (range 0.04–28.52), the median time to relapse was 12.2 years. A significant difference in duration of response was identified between patients that obtained a CR and PR (19.4 years versus 4.8 years, p
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- 2022
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5. Tixagevimab/Cilgavimab Pre-exposure Prophylaxis in Patients With Lymphoproliferative Disorders on BTKi
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Giulia Zamprogna, Anna Maria Frustaci, Giovanna Travi, Chiara Borella, Gianluigi Reda, Marina Motta, Marina Deodato, Elisa Bossi, Veronica Mattiello, Maria Beatrice Ferrari, Giulia Cotilli, Carlo Gambacorti-Passerini, Roberto Cairoli, Massimo Puoti, and Alessandra Tedeschi
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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6. Risk of hepatitis B virus reactivation in chronic lymphocytic leukemia patients receiving ibrutinib with or without antiviral prophylaxis. A retrospective multicentric GIMEMA study
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Idanna Innocenti, Gianluigi Reda, Andrea Visentin, Marta Coscia, Marina Motta, Roberta Murru, Riccardo Moia, Massimo Gentile, Elsa Pennese, Francesca Maria Quaglia, Francesco Albano, Ramona Cassin, Marina Deodato, Claudia Ielo, Anna Maria Frustaci, Alfonso Piciocchi, Arianna Rughini, Valentina Arena, Daniela Di Sevo, Annamaria Tomasso, Francesco Autore, Giovanni Del Poeta, Lydia Scarfò, Francesca Romana Mauro, Alessandra Tedeschi, Livio Trentin, Maurizio Pompili, Robin Foà, Paolo Ghia, Antonio Cuneo, and Luca Laurenti
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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7. Biological and clinical implications of BIRC3 mutations in chronic lymphocytic leukemia
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Fary Diop, Riccardo Moia, Chiara Favini, Elisa Spaccarotella, Lorenzo De Paoli, Alessio Bruscaggin, Valeria Spina, Lodovico Terzi-di-Bergamo, Francesca Arruga, Chiara Tarantelli, Clara Deambrogi, Silvia Rasi, Ramesh Adhinaveni, Andrea Patriarca, Simone Favini, Sruthi Sagiraju, Clive Jabangwe, Ahad A. Kodipad, Denise Peroni, Francesca R. Mauro, Ilaria Del Giudice, Francesco Forconi, Agostino Cortelezzi, Francesco Zaja, Riccardo Bomben, Francesca Maria Rossi, Carlo Visco, Annalisa Chiarenza, Gian Matteo Rigolin, Roberto Marasca, Marta Coscia, Omar Perbellini, Alessandra Tedeschi, Luca Laurenti, Marina Motta, David Donaldson, Phil Weir, Ken Mills, Patrick Thornton, Sarah Lawless, Francesco Bertoni, Giovanni Del Poeta, Antonio Cuneo, Antonia Follenzi, Valter Gattei, Renzo Luciano Boldorini, Mark Catherwood, Silvia Deaglio, Robin Foà, Gianluca Gaidano°, and Davide Rossi°
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
BIRC3 is a recurrently mutated gene in chronic lymphocytic leukemia (CLL) but the functional implications of BIRC3 mutations are largely unexplored. Furthermore, little is known about the prognostic impact of BIRC3 mutations in CLL cohorts homogeneously treated with first-line fludarabine, cyclophosphamide, and rituximab (FCR). By immunoblotting analysis, we showed that the non-canonical nuclear factor-κB pathway is active in BIRC3-mutated cell lines and in primary CLL samples, as documented by the stabilization of MAP3K14 and by the nuclear localization of p52. In addition, BIRC3-mutated primary CLL cells are less sensitive to flu-darabine. In order to confirm in patients that BIRC3 mutations confer resistance to fludarabine-based chemoimmunotherapy, a retrospective multicenter cohort of 287 untreated patients receiving first-line FCR was analyzed by targeted next-generation sequencing of 24 recurrently mutated genes in CLL. By univariate analysis adjusted for multiple comparisons BIRC3 mutations identify a poor prognostic subgroup of patients in whom FCR treatment fails (median progression-free survival: 2.2 years, P
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- 2020
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8. A phase II multi-center trial of pentostatin plus cyclophosphamide with ofatumumab in older previously untreated chronic lymphocytic leukemia patients
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Alessandra Tedeschi, Davide Rossi, Marina Motta, Giulia Quaresmini, Marianna Rossi, Marta Coscia, Antonella Anastasia, Fausto Rossini, Agostino Cortelezzi, Guido Nador, Lydia Scarfò, Roberto Cairoli, Anna Maria Frustaci, Daniela Dalceggio, Paola Picardi, Lorenzo De Paoli, Ester Orlandi, Alessandro Rambaldi, Massimo Massaia, Gianluca Gaidano, and Marco Montillo
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2015
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9. Bendamustine and subcutaneous alemtuzumab combination is an effective treatment in relapsed/refractory chronic lymphocytic leukemia patients
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Marco Montillo, Alessandra Tedeschi, Gianluca Gaidano, Marta Coscia, Valeria Belsito Petrizzi, Ester Orlandi, Nicola Cascavilla, Paolo Ghia, Marina Motta, Andrea Gallamini, Anna Maria Frustaci, Davide Rossi, Lorenzo De Paoli, Michele Nichelatti, Enrica Morra, and Massimo Massaia
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2014
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10. MINING, DEFORESTATION AND BURNING IN INDIGENOUS LANDS
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Gadelha, Marina Motta Benevides, primary
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- 2022
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11. Temas de Derecho Minero y Energético
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Ana Milena Vásquez Domínguez, Marina Motta Benevides Gadelha, Margarita Ricaurte Rueda, Diana Carolina Sánchez Zapata, Adriana María Sanín Vélez, Clara Inés Atehortúa Arredondo, Ana Restrepo Londoño, Laura Juanita Villanueva Marroquín, Sebastián Cabrales Villalba, Arenas A I Molina, C Guzmán E Ávila, Milton Fernando Montoya Pardo and Ana Milena Vásquez Domínguez, Marina Motta Benevides Gadelha, Margarita Ricaurte Rueda, Diana Carolina Sánchez Zapata, Adriana María Sanín Vélez, Clara Inés Atehortúa Arredondo, Ana Restrepo Londoño, Laura Juanita Villanueva Marroquín, Sebastián Cabrales Villalba, Arenas A I Molina, C Guzmán E Ávila, Milton Fernando Montoya Pardo
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- 2022
12. Differences in Clinical Course and Management of Sars-CoV2 Infection in Patients with Chronic Lymphocytic Leukemia between the Sequential Pandemic Phases: An Eric Study
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Andrea Visentin, Lydia Scarfò, Thomas Chatzikonstantinou, Anargyros Kapetanakis, Christos Demosthenous, Georgios Karakatsoulis, Martin Andres, Darko Antic, David Allsup, Mónica Baile, Dominique Bron, Antonella Capasso, Mark Catherwood, Rosa Collado, Raul Cordoba, Carolina Cuéllar-García, Julio Delgado, Maria Dimou, Michael Doubek, Lorenzo De Paoli, Maria Rosaria De Paolis, Giovanni Del Poeta, Maria Efstathopoulou, El-Ashwah Shimaa, Alicia Enrico, Lucia Farina, Angela Ferrari, Myriam Foglietta, Moritz Furstenau, Jose A. Garcia-Marco, Massimo Gentile, Eva Gimeno, Gomes da Silva Maria, Odit Gutwein, Yervand Hakobyan, Yair Herishanu, jose Angel Hernandez, Tobias Herold, Sunil Iyengar, Gilad Itchaki, Ozren Jaksic, Ann Janssens, Olga Kalashnikova, Elzbieta Kalicinska, Arnon P. Kater, Sabina Kersting, Jorge Labrador, Deepesh Lad, Luca Laurenti, Mark-David Levin, Enrico Lista, Lara Malerba, Roberto Marasca, Monia Marchetti, Juan Marquet Palomanes, Mattias Mattsson, Francesca Romana Mauro, Carlota Mayor-Bastida, Marta Morawska, Marina Motta, Talha Munir, Roberta Murru, Ivana Milosevic, Fatima Miras Calvo, Carsten Utoft Niemann, Jacopo Olivieri, Lorella Orsucci, Maria Papaioannou, Miguel Arturo Pavlovsky, Inga S. Piskunova, Barbara Pocali, Viola Maria Popov, Francesca Maria Quaglia, Giulia Quaresmini, Doreen te Raa, Gianluigi Reda, Gian Matteo Rigolin, Rosa Ruchlemer, Amit Shrestha, Martin Šimkovič, Martin Špaček, Paolo Sportoletti, Oana Stanca Ciocan, Tamar Tadmor, Elisabeth Vandenberghe, Marzia Varettoni, Candida Vitale, Ellen Van Der Spek, Michel Van Gelder, Ewa Wasik-Szczepanek, Lucrecia Yáñez, Mohamed A Yassin, Marta Coscia, Barbara Eichhorst, Alessandro Rambaldi, Niki Stavroyianni, Livio Trentin, Kostas Stamatopoulos, and Paolo Ghia
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
13. How Age, Comorbidities and Concomitant Medications Influence Ibrutinib Management and Survival in Waldenstrom Macroglobulinemia
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Annamaria Frustaci, Francesco Piazza, Simone Ferrero, Gianluigi Reda, Rita Rizzi, Lorella Orsucci, Isacco Ferrarini, Marina Deodato, Luca Laurenti, Benedetta Puccini, Claudia Baratè, Marzia Varettoni, Michele Merli, Emanuele Cencini, Antonino Greco, Guido Gini, Angela Ferrari, Chiara Borella, Enrico Lista, Massimo Gentile, Roberta Murru, Marina Motta, Francesca Rezzonico, Monica Tani, Paolo Sportoletti, Giulia Zamprogna, Valter Torri, Roberto Cairoli, and Alessandra Tedeschi
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
14. Not Yet Time to Retire Splenectomy in Splenic Marginal Zone Lymphoma (SMZL): Results of a Single Center Experience
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Antonella Anastasia, Chiara Pagani, Alessandro Re, Marina Motta, Giacomo Pata, Enrico Damiani, Lisa Gandolfi, Rosa Daffini, and Alessandra Tucci
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
15. Targeting the immune microenvironment in Waldenström Macroglobulinemia via halting the CD40/CD40-ligand axis
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Antonio Sacco, Vanessa Desantis, Jon Celay, Viviana Giustini, Fabio Rigali, Francesco D Savino, Michele Cea, Debora Soncini, Antonia Cagnetta, Antonio Giovanni Solimando, Deborah D'Aliberti, Silvia Spinelli, Daniele Ramazzotti, Camillo Almici, Katia Todoerti, Antonino Neri, Antonella Anastasia, Alessandra Tucci, Marina Motta, Marco Chiarini, Yawara Kawano, Jose-Al Martinez-Climent, Rocco Piazza, Aldo M Roccaro, Sacco, A, Desantis, V, Celay, J, Giustini, V, Rigali, F, Savino, F, Cea, M, Soncini, D, Cagnetta, A, Solimando, A, D'Aliberti, D, Spinelli, S, Ramazzotti, D, Almici, C, Todoerti, K, Neri, A, Anastasia, A, Tucci, A, Motta, M, Chiarini, M, Kawano, Y, Martinez-Climent, J, Piazza, R, and Roccaro, A
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Immunology ,Cell Biology ,Hematology ,Waldenström Macroglobulinemia ,Biochemistry - Abstract
Recent investigations have improved our understanding of the molecular aberrations supporting Waldenström macroglobulinemia (WM) biology; however, whether the immune microenvironment contributes to WM pathogenesis remains unanswered. First, we showed how a transgenic murine model of human-like lymphoplasmacytic lymphoma/WM exhibits an increased number of regulatory T cells (Tregs) relative to control mice. These findings were translated into the WM clinical setting, in which the transcriptomic profiling of Tregs derived from patients with WM unveiled a peculiar WM-devoted messenger RNA signature, with significant enrichment for genes related to nuclear factor κB–mediated tumor necrosis factor α signaling, MAPK, and PI3K/AKT, which was paralleled by a different Treg functional phenotype. We demonstrated significantly higher Treg induction, expansion, and proliferation triggered by WM cells, compared with their normal cellular counterpart; with a more profound effect within the context of CXCR4C1013G-mutated WM cells. By investigating the B-cell–to–T-cell cross talk at single-cell level, we identified the CD40/CD40-ligand as a potentially relevant axis that supports WM cell–Tregs interaction. Our findings demonstrate the existence of a Treg-mediated immunosuppressive phenotype in WM, which can be therapeutically reversed by blocking the CD40L/CD40 axis to inhibit WM cell growth.
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- 2023
16. Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and COVID-19: A study of ERIC, the European Research Initiative on CLL
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Darko Antic, Natasa Milic, Thomas Chatzikonstantinou, Lydia Scarfò, Vladimir Otasevic, Nina Rajovic, David Allsup, Alejandro Alonso Cabrero, Martin Andres, Monica Baile Gonzales, Antonella Capasso, Rosa Collado, Raul Cordoba, Carolina Cuéllar-García, Juan Gonzalo Correa, Lorenzo De Paoli, Maria Rosaria De Paolis, Giovanni Del Poeta, Maria Dimou, Michael Doubek, Maria Efstathopoulou, Shaimaa El-Ashwah, Alicia Enrico, Blanca Espinet, Lucia Farina, Angela Ferrari, Myriam Foglietta, Alberto Lopez-Garcia, José A. García-Marco, Rocío García-Serra, Massimo Gentile, Eva Gimeno, Maria Gomes Silva, Odit Gutwein, Yervand K. Hakobyan, Yair Herishanu, José Ángel Hernández-Rivas, Tobias Herold, Gilad Itchaki, Ozren Jaksic, Ann Janssens, Оlga B. Kalashnikova, Elżbieta Kalicińska, Arnon P. Kater, Sabina Kersting, Maya Koren-Michowitz, Jorge Labrador Gomez, Deepesh Lad, Luca Laurenti, Alberto Fresa, Mark-David Levin, Carlota Mayor Bastida, Lara Malerba, Roberto Marasca, Monia Marchetti, Juan Marquet, Biljana Mihaljevic, Ivana Milosevic, Fatima Mirás, Marta Morawska, Marina Motta, Talha Munir, Roberta Murru, Raquel Nunes, Jacopo Olivieri, Miguel Arturo Pavlovsky, Inga Piskunova, Viola Maria Popov, Francesca Maria Quaglia, Giulia Quaresmini, Gianluigi Reda, Gian Matteo Rigolin, Amit Shrestha, Martin Šimkovič, Svetlana Smirnova, Martin Špaček, Paolo Sportoletti, Oana Stanca, Niki Stavroyianni, Doreen Te Raa, Kristina Tomic, Sanne Tonino, Livio Trentin, Ellen Der Spek, Michel Gelder, Marzia Varettoni, Andrea Visentin, Candida Vitale, Vojin Vukovic, Ewa Wasik-Szczepanek, Tomasz Wróbel, Lucrecia Yáñez San Segundo, Mohamed Yassin, Marta Coscia, Alessandro Rambaldi, Emili Montserrat, Robin Foà, Antonio Cuneo, Marc Carrier, Paolo Ghia, and Kostas Stamatopoulos
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Background: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. In this retrospective multicenter study, conducted by ERIC, the European Research Initiative on CLL, we assessed the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19.Methods: The study included patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021.Results: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 518 were defined as having severe COVID: 162 were admitted to the ICU while 356 received oxygen supplementation outside the ICU. Most patients (90%) were receiving thromboprophylaxis. During COVID-19 treatment, 8.8% developed a thromboembolic event, while 4.8% experienced bleeding. Thrombosis developed in 20.5% of patients who were not receiving thromboprophylaxis, but only in 8.1% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (11.1% vs. 4.2%, respectively) and in elderly. In multivariate analysis, peak D-dimer level was a poor prognostic factor for thrombosis occurrence (OR=1.020, 95%CI 1.006‒1.033), while thromboprophylaxis use was protective (OR=0.194, 95%CI 0.061‒0.614). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR=1.055, 95%CI 1.013-1.103 and OR=2.490, 95%CI 1.044-5.935, respectively). Conclusions: Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.
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- 2022
17. Worldwide Examination of Patients with CLL Hospitalized for COVID-19
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Lindsey E Roeker, Lydia Scarfo, Thomas Chatzikonstantinou, Pau Abrisqueta, Toby A. Eyre, Raul Cordoba, Ana Muntañola Prat, Guillermo Villacampa, Lori A. Leslie, Michael Koropsak, Giulia Quaresmini, John N. Allan, Richard R. Furman, Erica B Bhavsar, John M. Pagel, Jose Angel Hernandez-Rivas, Krish Patel, Marina Motta, Neil Bailey, Fatima Miras, Nicole Lamanna, Rosalia Alonso, Santiago Osorio-Prendes, Candida Vitale, Manali Kamdar, Patricia Baltasar, Anders Österborg, Lotta Hanson, Mónica Baile, Ines Rodríguez-Hernández, Susana Valenciano, Viola Maria Popov, Abelardo Barez Garcia, Ana Alfayate, Ana C Oliveira, Barbara Eichhorst, Francesca M. Quaglia, Gianluigi Reda, Javier Lopez Jimenez, Marzia Varettoni, Monia Marchetti, Pilar Romero, Rosalía Riaza Grau, Talha Munir, Amaya Zabalza, Ann Janssens, Carsten U Niemann, Guilherme Fleury Perini, Julio Delgado, Lucrecia Yanez San Segundo, Ma Isabel Gómez Roncero, Matthew Wilson, Piers Patten, Roberto Marasca, Sunil Iyengar, Amanda Seddon, Ana Torres, Angela Ferrari, Carolina Cuéllar-García, Daniel Wojenski, Dima El-Sharkawi, Gilad Itchaki, Helen Parry, Juan José Mateos-Mazón, Nicolas Martinez-Calle, Shuo Ma, Daniel Naya, Ellen Van Der Spek, Erlene K. Seymour, Eva Gimeno Vázquez, Gian Matteo Rigolin, Francesca Romana Mauro, Harriet S Walter, Jorge Labrador, Lorenzo De Paoli, Luca Laurenti, Elena Ruiz, Mark-David Levin, Martin Šimkovič, Martin Špaček, Rafa Andreu, Renata Walewska, Sonia Perez-Gonzalez, Suchitra Sundaram, Adrian Wiestner, Amalia Cuesta, Angus Broom, Arnon P. Kater, Begoña Muiña, César A Velasquez, Chaitra S. Ujjani, Cristina Seri, Darko Antic, Dominique Bron, Elisabeth Vandenberghe, Elise A. Chong, Enrico Lista, Fiz Campoy García, Giovanni Del Poeta, Inhye Ahn, Jeffrey J. Pu, Jennifer R Brown, Juan Alfonso Soler Campos, Lara Malerba, Livio Trentin, Lorella Orsucci, Lucia Farina, Lucia Villalon, Maria Jesus Vidal, Maria Jose Sanchez, Maria Jose Terol, Maria Rosaria De Paolis, Massimo Gentile, Matthew S. Davids, Mazyar Shadman, Mohamed A Yassin, Myriam Foglietta, Ozren Jaksic, Paolo Sportoletti, Paul M. Barr, Rafael Ramos, Raquel Santiago, Rosa Ruchlemer, Sabina Kersting, Scott F. Huntington, Tobias Herold, Yair Herishanu, Meghan C. Thompson, Sonia Lebowitz, Christine Ryan, Ryan W. Jacobs, Craig A. Portell, Krista Isaac, Alessandro Rambaldi, Chadi Nabhan, Danielle M. Brander, Emili Montserrat, Giuseppe Rossi, Jose A. Garcia-Marco, Marta Coscia, Nikita Malakhov, Noemi Fernandez-Escalada, Sigrid Strand Skånland, Callie C. Coombs, Paola Ghione, Stephen J. Schuster, Robin Foà, Antonio Cuneo, Francesc Bosch, Kostas Stamatopoulos, Paolo Ghia, Anthony R. Mato, and Meera Patel
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education.field_of_study ,medicine.medical_specialty ,business.industry ,Proportional hazards model ,Venetoclax ,902.Health Services Research-Malignant Conditions (Lymphoid Disease) ,Immunology ,Population ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,chemistry.chemical_compound ,chemistry ,Chemoimmunotherapy ,Internal medicine ,Case fatality rate ,Cohort ,Clinical endpoint ,Medicine ,Lymphocytopenia ,education ,business - Abstract
Introduction: Patients (pts) with CLL may be at particular risk of severe COVID-19 given advanced age and immune dysregulation. Two large series with limited follow-up have reported outcomes for pts with CLL and COVID-19 (Scarfò, et al. Leukemia 2020; Mato, et al. Blood 2020). To provide maximal clarity on outcomes for pts with CLL and COVID-19, we partnered in a worldwide effort to describe the clinical experience and validate predictors of survival, including potential treatment effects. Methods: This international collaboration represents a partnership between investigators at 141 centers. Data are presented in two cohorts. Cohort 1 (Co1) includes pts captured through efforts by European Research Initiative on CLL (ERIC), Italian CAMPUS CLL Program, and Grupo Español de Leucemia Linfática Crónica. The validation cohort, Cohort 2 (Co2), includes pts from US (66%), UK (23%), EU (7%), and other countries (4%). There is no overlap in cases between cohorts. CLL pts were included if COVID-19 was diagnosed by PCR detection of SARS-CoV-2 and they required inpatient hospitalization. Data were collected retrospectively 2/2020 - 5/2020 using standardized case report forms. Baseline characteristics, preexisting comorbidities (including cumulative illness rating scale (CIRS) score ≥6 vs. The primary endpoint of this study was to estimate the case fatality rate (CFR), defined as the proportion of pts who died among all pts hospitalized with COVID-19. Chi-squared test was used to compare frequencies; univariable and multivariable analyses utilized Cox regression. Predictors of inferior OS in both Co1 and Co2 were included in multivariable analyses. Kaplan-Meier method was used to estimate overall survival (OS) from time of COVID-19 diagnosis (dx). Results: 411 hospitalized, COVID-19 positive CLL pts were analyzed (Co1 n=281, Co2 n=130). Table 1 describes baseline characteristics. At COVID-19 dx, median age was 72 in Co1 (range 37-94) and 68 in Co2 (range 41-98); 31% (Co1) and 45% (Co2) had CIRS ≥6. In Co1, 48% were treatment-naïve and 26% were receiving CLL-directed therapy at COVID-19 dx (66% BTKi ± anti-CD20, 19% Venetoclax ± anti-CD20, 9.6% chemo/chemoimmunotherapy (CIT), 1.4% PI3Ki, 4% other). In Co2, 36% were never treated and 49% were receiving CLL-directed therapy (65% BTKi ± anti-CD20, 19% Venetoclax ± anti-CD20, 9.4% multi-novel agent combinations, 1.6% CIT, 1.6% PI3Ki, 1.6% anti-CD20 monotherapy, 1.6% other). Most pts receiving CLL-directed therapy had it held at COVID-19 diagnosis (93% in Co1 and 81% in Co2). Frequency of most COVID-19 symptoms/laboratory abnormalities were similar in the two cohorts including fever (88% in both), lymphocytosis (ALC ≥30 x 109/L; 27% vs. 21%), and lymphocytopenia (ALC < 1.0 x 109/L; 18% vs. 28%), while others varied between Co1 and Co2 (p Median follow-up was 24 days (range 2-86) in Co1 and 17 days (1-43) in Co2. CFRs were similar in Co1 and Co2, 30% and 34% (p=0.45). 54% and 43% were discharged while 16% and 23% remained admitted at last follow-up in Co1 and Co2, respectively. The proportion of pts requiring supplemental oxygen was similar (89% vs. 92%) while rate of ICU admission was higher in Co2 (20% vs. 48%, p Conclusions : In the largest cancer dx-specific cohort reported, pts with CLL hospitalized for COVID-19 had a CFR of 30-34%. Advanced patient age at COVID-19 diagnosis was an independent predictor of OS in two large cohorts. This CFR will serve as a benchmark for mortality for future outcomes studies, including therapeutic interventions for COVID-19 in this population. The effect of CLL treatment on OS was inconsistent across cohorts; COVID-19 may be severe regardless of treatment status. While there were no significant differences in distribution of current lines of therapy between cohorts, prior chemo exposure was more common in Co1 vs. Co2, which may account for difference in OS. Extended follow-up will be presented. Disclosures Roeker: American Society of Hematology: Research Funding; Abbott Laboratories: Other: spouse with minority ownership interest ; AbbVie: Other: spouse with minority ownership interest . Scarfo:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees. Abrisqueta:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; AbbVie: Consultancy, Honoraria, Speakers Bureau. Eyre:AbbVie: Consultancy, Honoraria, Other: travel support; Gilead: Consultancy, Honoraria, Other: travel support; Janssen: Consultancy, Honoraria, Other: travel support; KITE, AZ, Loxo Oncology at Lilly: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Muntañola Prat:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants; participated in advisory boards; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants; participated in advisory boards; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants; participated in advisory boards. Villacampa:AstraZeneca: Other: advisory role; Merck Sharp & Dohme: Honoraria. Leslie:AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; ADC therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Speakers Bureau; KitePharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene/BMS: Speakers Bureau; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pharmacyclics/Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Epizyme: Speakers Bureau; Karyopharm: Speakers Bureau; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Allan:Acerta, Genentech, Abbvie, Sunesis, Ascentage, Pharmacyclics, Janssen, AstraZeneca, BeiGene: Consultancy; Celgene, Genentech, Janssen, TG Therapeutics: Research Funding; Abbvie, Janssen, AstraZeneca, Pharmacyclics: Honoraria. Furman:Incyte: Consultancy; Genentech: Consultancy; Sunesis: Consultancy; Pharmacyclics: Consultancy; Loxo Oncology: Consultancy; Oncotarget: Consultancy; Janssen: Consultancy, Speakers Bureau; TG Therapeutics: Consultancy, Research Funding; Abbvie: Consultancy; Beigene: Consultancy; AstraZeneca: Consultancy, Research Funding; Acerta: Consultancy; Verastem: Consultancy. Pagel:BeiGene, Astrazeneca, Loxo Oncology, Gilead: Consultancy. Hernandez-Rivas:Gilead: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Rovi: Membership on an entity's Board of Directors or advisory committees. Patel:Genentech: Consultancy, Speakers Bureau; Adaptive Biotechnologies: Consultancy; Janssen: Consultancy, Speakers Bureau; Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy; Kite: Consultancy; Pharmacyclics: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Research Funding, Speakers Bureau. Motta:Roche: Honoraria; Janssen: Honoraria. Lamanna:AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Verastem: Research Funding; Bei-Gene: Research Funding; TG Therapeutics: Research Funding; Acerta: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche-Genentech: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Vitale:Janssen: Honoraria. Kamdar:Roche: Research Funding. Österborg:BeiGene: Research Funding; Kancera: Current equity holder in publicly-traded company, Research Funding; Sanofi: Consultancy; Karolinska Univeristy Hospital, Stockholm, Sweden: Current Employment. Hanson:Janssen-Cilag: Research Funding; Gilead: Research Funding; AbbVie: Honoraria. Eichhorst:ArQule: Consultancy, Honoraria, Other: travel support, Research Funding; BeiGene: Consultancy, Honoraria, Other: travel support, Research Funding; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: travel support, Research Funding; Oxford Biomedica: Consultancy, Honoraria, Other: travel support, Research Funding; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding; F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding; Novartis: Consultancy, Honoraria, Other: travel support, Research Funding. Reda:Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees. Varettoni:Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel/accommodations/expenses; AbbVie: Other: Travel/accommodations/expenses; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees. Marchetti:Gilead: Consultancy; Novartis: Speakers Bureau; Amgen: Speakers Bureau; AbbVie: Other: Sponsored meetings; Takeda: Other: Sponsored meetings; Pfeizer: Other: Sponsored meetings. Munir:F. Hoffmann-La Roche: Consultancy, Other: Medical writing support, furnished by Scott Battle, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland; Alexion: Honoraria. Zabalza:Janssen: Honoraria, Other: travel grants; Roche: Other: travel grants; Novartis: Other: travel grants. Janssens:Amgen: Consultancy, Other: travel grants; speaker fees; Abbvie: Consultancy, Other: travel grants; speaker fees; Celgene: Consultancy, Other: travel grants; speaker fees; Janssen: Consultancy, Other: travel grants; speaker fees; Gilead: Consultancy, Other: travel grants; speaker fees; Novartis: Consultancy, Other: travel grants; speaker fees; Sanofi-Genzyme: Consultancy, Other: travel grants; speaker fees; Roche: Consultancy, Other: travel grants; speaker fees. Niemann:AstraZeneca: Honoraria, Research Funding; CSL Behring: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Sunesis: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Danish Cancer Society: Honoraria, Research Funding; Novo Nordisk Foundation: Honoraria, Research Funding. Perini:Takeda: Honoraria; Janssen: Honoraria, Speakers Bureau; Abbvie: Speakers Bureau. Patten:AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra Zeneca: Honoraria. Marasca:Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Honoraria. Iyengar:Janssen: Honoraria; Gilead: Honoraria. Ferrari:Abbvie: Honoraria. El-Sharkawi:Roche: Other: Conference fees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Itchaki:Abbvie Inc: Consultancy, Research Funding. Ma:Novartis: Research Funding; Juno: Research Funding; Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; Kite: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Bioverativ: Consultancy, Honoraria; BeiGene: Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Research Funding; TG Therapeutics: Research Funding. Van Der Spek:AMGEN: Other: Teaching activities. Seymour:Seattle Genetics: Research Funding; Merck: Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen/Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; Genentech: Research Funding; Bristol-Myers Squibb: Research Funding. Rigolin:Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Mauro:Roche: Other; Octopharma: Other; Takeda-Shire: Other; Gilead: Other; Janssen: Other; Abbvie: Other. Laurenti:Janssen: Honoraria; Gilead: Honoraria; AbbVie: Honoraria; Roche: Honoraria. Levin:Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel compensation; Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: travel compensation; Roche: Membership on an entity's Board of Directors or advisory committees, Other: travel compensation. Špaček:Gilead: Honoraria; Abbvie: Honoraria; Janssen: Honoraria. Walewska:AbbVie: Other: sponsored for educational meetings, Speakers Bureau; Janssen: Other: sponsored for educational meetings, Speakers Bureau; Gilead: Speakers Bureau; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees. Wiestner:Pharmacyclics LLC, an AbbVie Company; Acerta, Merck, Nurix, Verastem, and Genmab: Research Funding; National Institutes of Health: Patents & Royalties: and other intellectual property. Broom:Gilead: Other: Travel support, Speakers Bureau. Kater:Abbvie: Research Funding; Roche: Research Funding; Janssen: Research Funding; Celgene: Research Funding; Genentech: Research Funding. Ujjani:AstraZeneca: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Verastem Oncology: Consultancy, Honoraria; Gilead/Kite: Consultancy, Research Funding; Atara: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; MorphoSys: Consultancy. Vandenberghe:Celgene: Other: sponsorship to attend Lugano lymphoma meeting in 2019; Gilead: Other: travel grants, Research Funding; Abbvie: Other: travel grants, Research Funding; Janssen: Other: travel grants; Roche: Other: travel grants, Research Funding. Chong:Novartis: Membership on an entity's Board of Directors or advisory committees; Tessa: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; KITE Pharma: Membership on an entity's Board of Directors or advisory committees. Pu:Takeda Pharmaceuticals: Consultancy. Brown:Janssen, Teva: Speakers Bureau; Gilead, Loxo, Sun, Verastem: Research Funding; Abbvie, Acerta, AstraZeneca, Beigene, Invectys, Juno/Celgene, Kite, Morphosys, Novartis, Octapharma, Pharmacyclics, Sunesis, TG Therapeutics, Verastem: Consultancy. Trentin:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Octapharma: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Shire: Honoraria. Farina:Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Sanchez:Abbvie: Other: travel grants; Amgem: Other: travel grants; Janssen: Other: travel grants; Celgene: Other: travel grants; Roche: Other: travel grants. Shadman:Abbvie, Genentech, Astra Zeneca, Sound Biologics , Pharmacyclics, Verastem, ADC therapeutics, Beigene, Cellectar, BMS, Morphosys and Atara Biotherapeutics: Consultancy; Mustang Bio, Celgene, Pharmacyclics, Gilead, Genentech, Abbvie, TG therapeutics, Beigene, Astra Zeneca, Sunesis, Beigene: Research Funding. Foglietta:Janssen: Honoraria; Gilead: Honoraria. Jaksic:Roche: Honoraria; Janssen: Honoraria; Abbvie: Honoraria. Sportoletti:AbbVie: Honoraria; Janssen: Honoraria. Barr:Morphosys: Consultancy; Gilead: Consultancy; AstraZeneca: Consultancy, Research Funding; Verastem: Consultancy; Seattle Genetics: Consultancy; TG therapeutics: Consultancy, Research Funding; Abbvie/Pharmacyclics: Consultancy, Research Funding; Celgene: Consultancy; Merck: Consultancy; Genentech: Consultancy; Janssen: Consultancy. Ruchlemer:Abbvie Inc: Consultancy, Research Funding. Kersting:Celgene: Other: travel grant; Janssen: Research Funding; Abbvie: Research Funding. Huntington:Pharmacyclics: Honoraria; AbbVie: Consultancy; Novartis: Consultancy; Genentech: Consultancy; DTRM: Research Funding; Celgene: Consultancy, Research Funding; Bayer: Consultancy, Honoraria; Astrazeneca: Honoraria; TG Therapeutics: Research Funding. Herishanu:Roche: Honoraria; Sanofi: Honoraria; Medison: Honoraria; Janssen: Honoraria; Abbvie: Honoraria; AstraZeneca: Honoraria. Jacobs:TG Therapeutics, Inc.: Research Funding; Astra Zeneca: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau; Pharmacyclics: Research Funding, Speakers Bureau; Seattle Genetics: Consultancy; Verastem: Consultancy; Janssen: Consultancy, Speakers Bureau; Genentech: Speakers Bureau; Sanofi Genzyme: Speakers Bureau. Portell:BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy; TG Therapeutics: Research Funding; Infinity: Research Funding; Roche/Genentech: Consultancy, Research Funding; Xencor: Research Funding; Bayer: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding; AbbVie: Research Funding. Rambaldi:Sanofi: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Astellas: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); BMS/Celgene: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); University of Milan: Current Employment; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support of parent study and funding of editorial support. Received travel support., Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support from Gilead.; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Research grant from Amgen Inc.; Omeros: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Advisory board and speaker fees from Pfizer.. Brander:Verastem: Consultancy, Honoraria, Other, Research Funding; NCCN: Other; Novartis: Consultancy, Other; Teva: Consultancy, Honoraria; Tolero: Research Funding; NCCN: Other; Novartis: Consultancy, Other; Teva: Consultancy, Honoraria; Tolero: Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; ArQule: Consultancy, Other, Research Funding; Ascentage: Other, Research Funding; AstraZeneca: Consultancy, Honoraria, Other, Research Funding; BeiGene: Other, Research Funding; DTRM: Other, Research Funding; Genentech: Consultancy, Honoraria, Other, Research Funding; Juno/Celgene/BMS: Other, Research Funding; MEI Pharma: Other, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Other, Research Funding; Pfizer: Consultancy, Other; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding. Rossi:Abbvie: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Advisory board; Astellas: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Coscia:Karyopharm Therapeutics: Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Coombs:Abbvie: Consultancy, Honoraria; Genentech: Honoraria; AstraZeneca: Honoraria; MEI Pharma: Honoraria; LOXO Oncology: Honoraria; Octapharma: Honoraria; Novartis: Honoraria. Schuster:Novartis, Genentech, Inc./ F. Hoffmann-La Roche: Research Funding; AlloGene, AstraZeneca, BeiGene, Genentech, Inc./ F. Hoffmann-La Roche, Juno/Celgene, Loxo Oncology, Nordic Nanovector, Novartis, Tessa Therapeutics: Consultancy, Honoraria. Foà:Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Incyte: Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Cuneo:Astra Zeneca: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Bosch:Jansen: Honoraria; Abbvie: Honoraria; Novartis: Honoraria; Astra Zeneca: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Roche: Honoraria. Stamatopoulos:AstraZeneca: Honoraria; Janssen, Gilead, Abbvie: Honoraria, Research Funding. Ghia:Adaptive, Dynamo: Consultancy, Honoraria; Novartis: Research Funding; BeiGene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Celgene/Juno: Consultancy, Honoraria; Lilly: Consultancy, Honoraria; MEI: Consultancy, Honoraria; Sunesis: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Gilead: Consultancy, Honoraria, Research Funding; ArQule: Consultancy, Honoraria; Acerta/AstraZeneca: Consultancy, Honoraria. Mato:Adaptive: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; BeiGene: Consultancy; LOXO: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; TG Therapeutics: Consultancy, Other: DSMB, Research Funding.
- Published
- 2020
18. Preneoplastic somatic mutations including
- Author
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Sara, Rodriguez, Jon, Celay, Ibai, Goicoechea, Cristina, Jimenez, Cirino, Botta, Maria-José, Garcia-Barchino, Juan-Jose, Garces, Marta, Larrayoz, Susana, Santos, Diego, Alignani, Amaia, Vilas-Zornoza, Cristina, Perez, Sonia, Garate, Sarai, Sarvide, Aitziber, Lopez, Hans-Christian, Reinhardt, Yolanda R, Carrasco, Isidro, Sanchez-Garcia, Maria-Jose, Larrayoz, Maria-Jose, Calasanz, Carlos, Panizo, Felipe, Prosper, Jose-Maria, Lamo-Espinosa, Marina, Motta, Alessandra, Tucci, Antonio, Sacco, Massimo, Gentile, Sara, Duarte, Helena, Vitoria, Catarina, Geraldes, Artur, Paiva, Noemi, Puig, Ramon, Garcia-Sanz, Aldo M, Roccaro, Gema, Fuerte, Jesus F, San Miguel, Jose-Angel, Martinez-Climent, and Bruno, Paiva
- Subjects
Lymphoma, B-Cell ,Lymphoma ,SciAdv r-articles ,Diseases and Disorders ,Mice ,hemic and lymphatic diseases ,Mutation ,Myeloid Differentiation Factor 88 ,Animals ,Humans ,Biomedicine and Life Sciences ,Waldenstrom Macroglobulinemia ,Aged ,Research Article ,Cancer - Abstract
Normal cell counterparts of solid and myeloid tumors accumulate mutations years before disease onset; whether this occurs in B lymphocytes before lymphoma remains uncertain. We sequenced multiple stages of the B lineage in elderly individuals and patients with lymphoplasmacytic lymphoma, a singular disease for studying lymphomagenesis because of the high prevalence of mutated MYD88. We observed similar accumulation of random mutations in B lineages from both cohorts and unexpectedly found MYD88L265P in normal precursor and mature B lymphocytes from patients with lymphoma. We uncovered genetic and transcriptional pathways driving malignant transformation and leveraged these to model lymphoplasmacytic lymphoma in mice, based on mutated MYD88 in B cell precursors and BCL2 overexpression. Thus, MYD88L265P is a preneoplastic event, which challenges the current understanding of lymphomagenesis and may have implications for early detection of B cell lymphomas., Description, MYD88L265P occurs in between a normal mutated lymphopoiesis and additional genetic alterations during lymphomagenesis.
- Published
- 2022
19. Long-term benefit of IGHV mutated patients in a real-life multicenter cohort of FCR-treated chronic lymphocytic leukemia
- Author
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Riccardo Moia, Riccardo Dondolin, Maria Stefania De Propris, Donatella Talotta, Samir Mouhssine, Francesca Perutelli, Gianluigi Reda, Veronica Mattiello, Gian Matteo Rigolin, Marina Motta, Jacopo Olivieri, Renato Fanin, Omar Perbellini, Isacco Ferrarini, Francesca Romana Mauro, Ilaria Del Giudice, Luca Laurenti, Annamaria Tomasso, Massimo Gentile, Anna Maria Frustaci, Alessandra Tedeschi, Alessandro Gozzetti, Caterina Stelitano, Carlo Visco, Carol Moreno, Francesco Forconi, Roberto Marasca, Marta Coscia, Davide Rossi, Robin Foà, and Gianluca Gaidano
- Subjects
Cancer Research ,IGHV ,Settore MED/15 - MALATTIE DEL SANGUE ,Oncology ,FCR ,chronic lymphocytic leukemia ,Hematology ,General Medicine ,chronic lymphocytic leukemia, FCR, IGHV - Published
- 2022
20. Preneoplastic somatic mutations including MYD88(L265P) in lymphoplasmacytic lymphoma
- Author
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Sara Rodriguez, Jon Celay, Ibai Goicoechea, Cristina Jimenez, Cirino Botta, Maria-José Garcia-Barchino, Juan-Jose Garces, Marta Larrayoz, Susana Santos, Diego Alignani, Amaia Vilas-Zornoza, Cristina Perez, Sonia Garate, Sarai Sarvide, Aitziber Lopez, Hans-Christian Reinhardt, Yolanda R. Carrasco, Isidro Sanchez-Garcia, Maria-Jose Larrayoz, Maria-Jose Calasanz, Carlos Panizo, Felipe Prosper, Jose-Maria Lamo-Espinosa, Marina Motta, Alessandra Tucci, Antonio Sacco, Massimo Gentile, Sara Duarte, Helena Vitoria, Catarina Geraldes, Artur Paiva, Noemi Puig, Ramon Garcia-Sanz, Aldo M. Roccaro, Gema Fuerte, Jesus F. San Miguel, Jose-Angel Martinez-Climent, Bruno Paiva, Rodriguez, Sara, Celay, Jon, Goicoechea, Ibai, Jimenez, Cristina, Botta, Cirino, Garcia-Barchino, Maria-José, Garces, Juan-Jose, Larrayoz, Marta, Santos, Susana, Alignani, Diego, Vilas-Zornoza, Amaia, Perez, Cristina, Garate, Sonia, Sarvide, Sarai, Lopez, Aitziber, Reinhardt, Hans-Christian, Carrasco, Yolanda R, Sanchez-Garcia, Isidro, Larrayoz, Maria-Jose, Calasanz, Maria-Jose, Panizo, Carlo, Prosper, Felipe, Lamo-Espinosa, Jose-Maria, Motta, Marina, Tucci, Alessandra, Sacco, Antonio, Gentile, Massimo, Duarte, Sara, Vitoria, Helena, Geraldes, Catarina, Paiva, Artur, Puig, Noemi, Garcia-Sanz, Ramon, Roccaro, Aldo M, Fuerte, Gema, San Miguel, Jesus F, Martinez-Climent, Jose-Angel, and Paiva, Bruno
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Multidisciplinary ,hemic and lymphatic diseases ,Lymphoplasmacytic lymphoma ,lymphoplasmacytic lymphoma ,MYD88 ,Mutations ,B cell lymphoma ,single cell - Abstract
Normal cell counterparts of solid and myeloid tumors accumulate mutations years before disease onset; whether this occurs in B lymphocytes before lymphoma remains uncertain. We sequenced multiple stages of the B lineage in elderly individuals and patients with lymphoplasmacytic lymphoma, a singular disease for studying lymphomagenesis because of the high prevalence of mutated MYD88 . We observed similar accumulation of random mutations in B lineages from both cohorts and unexpectedly found MYD88 L265P in normal precursor and mature B lymphocytes from patients with lymphoma. We uncovered genetic and transcriptional pathways driving malignant transformation and leveraged these to model lymphoplasmacytic lymphoma in mice, based on mutated MYD88 in B cell precursors and BCL2 overexpression. Thus, MYD88 L265P is a preneoplastic event, which challenges the current understanding of lymphomagenesis and may have implications for early detection of B cell lymphomas.
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- 2022
21. Direct-Acting Antivirals as Primary Treatment for Hepatitis C Virus-Associated Indolent Non-Hodgkin Lymphomas: The BArT Study of the Fondazione Italiana Linfomi
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Michele, Merli, Sara, Rattotti, Michele, Spina, Francesca, Re, Marina, Motta, Piazza, Francesco, Lorella, Orsucci, Andrés J, M Ferreri, Omar, Perbellini, Anna, Dodero, Daniele, Vallisa, Alessandro, Pulsoni, Armando, Santoro, Paolo, Sacchi, Valentina, Zuccaro, Emanuela, Chimienti, Filomena, Russo, Carlo, Visco, Anna Linda Zignego, Luigi, Marcheselli, Francesco, Passamonti, Stefano, Luminari, Marco, Paulli, Raffaele, Bruno, and Luca, Arcaini
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Cancer Research ,Oncology ,Lymphoma ,Lymphoma, Non-Hodgkin ,HCV ,Humans ,HCV, Non Hodgkin Lymphoma, Direct-acting Antivirals ,Non Hodgkin Lymphoma ,Hepacivirus ,Hepatitis C, Chronic ,Antiviral Agents ,Direct-acting Antivirals ,Aged - Abstract
PURPOSE We prospectively treated patients with hepatitis C virus (HCV)–associated indolent lymphomas with genotype-appropriate direct-acting antivirals (DAAs) with the aim to evaluate virologic and hematologic outcomes. No prospective studies in this setting have been published so far. METHODS FIL_BArT is a prospective, multicenter, phase II trial that evaluated genotype-appropriate DAAs in untreated HCV-positive patients with indolent lymphomas without criteria for immediate conventional antilymphoma treatment. The primary objective was sustained virologic response, whereas the main secondary objectives were overall response rate of lymphoma and progression-free survival. RESULTS Forty patients were enrolled, including 27 with marginal zone lymphoma. Median age was 68 years. Extranodal sites were involved in 14 cases (35%). Main genotypes were 1 in 16 patients and 2 in 21 patients. All patients received genotype-guided DAAs: 17 ledipasvir/sofosbuvir, eight sofosbuvir plus ribavirin, and 15 sofosbuvir/velpatasvir. All patients achieved sustained virologic response (100%). DAAs were well tolerated, with only two grade 3-4 adverse events. Overall response rate of lymphoma was 45%, including eight patients (20%) achieving complete response and 10 (25%) partial response, whereas 16 exhibited stable disease and six progressed. With a median follow-up of 37 months, two patients died (3-year overall survival 93%; 95% CI, 74 to 98) and three additional patients progressed, with a 3-year progression-free survival of 76% (95% CI, 57 to 87). CONCLUSION HCV eradication by DAAs was achieved in 100% of HCV-positive patients with indolent lymphomas not requiring immediate conventional treatment and resulted in non-negligible rate of lymphoma responses. Treatment with DAAs should be considered as the first-line therapy in this setting.
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- 2022
22. Minimal residual disease–driven treatment intensification with sequential addition of ibrutinib to venetoclax in R/R CLL
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Lydia Scarfò, Silvia Heltai, Elisa Albi, Eloise Scarano, Luana Schiattone, Lucia Farina, Riccardo Moia, Marina Deodato, Andrea Ferrario, Marina Motta, Gianluigi Reda, Rosaria Sancetta, Marta Coscia, Paolo Rivela, Luca Laurenti, Marzia Varettoni, Eleonora Perotta, Antonella Capasso, Pamela Ranghetti, Maria Colia, and Paolo Ghia
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Settore MED/15 - MALATTIE DEL SANGUE ,Neoplasm, Residual ,Pyrimidines ,Minimal residual disease ,Immunology ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Pyrazoles ,Cell Biology ,Hematology ,Bridged Bicyclo Compounds, Heterocyclic ,Biochemistry ,Leukemia, Lymphocytic, Chronic, B-Cell - Abstract
Undetectable measurable residual disease (uMRD) is achievable in patients with chronic lymphocytic leukemia (CLL) with the BCL2-inhibitor venetoclax alone or combined with the Bruton’s tyrosine kinase inhibitor ibrutinib. This phase 2, multicenter, MRD-driven study was designed to discontinue treatment upon reaching uMRD4 (
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- 2022
23. How COVID-19 pandemic changed our attitude to venetoclax-based treatment in chronic lymphocytic leukemia
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Marina Deodato, Anna Maria Frustaci, Paolo Sportoletti, Luca Laurenti, Roberta Murru, Andrea Visentin, Gianluigi Reda, Francesca Romana Mauro, Giulia Quaresmini, Anna Vanazzi, Candida Vitale, Lorella Orsucci, Massimo Massaia, Alessandro Sanna, Marina Motta, Adalberto Ibatici, Isacco Ferrarini, Chiara Borella, Marzia Varettoni, Monica Tani, Sara Marinoni, Andrea Ferrario, Giulia Zamprogna, Marco Montillo, and Alessandra Tedeschi
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Sulfonamides ,Cancer Research ,venetoclax ,COVID-19 ,Hematology ,Bridged Bicyclo Compounds, Heterocyclic ,Leukemia, Lymphocytic, Chronic, B-Cell ,Settore MED/15 - MALATTIE DEL SANGUE ,Oncology ,Chronic lymphocytic leukemia ,Rituximab ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Pandemics - Published
- 2022
24. COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study
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Ellen van der Spek, Emili Montserrat, Talha Munir, Paolo Ghia, Shaimaa El-Ashwah, Andreas Glenthøj, Viola Maria Popov, Sanne H. Tonino, Ann Janssens, Michel van Gelder, Lara Malerba, Rocío García-Serra, Alberto Lopez-Garcia, Juan-Gonzalo Correa, Christos Demosthenous, Idanna Innocenti, Maria Papaioannou, Lydia Scarfò, Antonio Cuneo, Francesca Romana Mauro, Sabina Kersting, Robin Foà, David Donaldson, Livio Trentin, Roberta Murru, Panagiotis Baliakas, Marina Motta, Deepesh Lad, Yervand K Hakobyan, Paolo Sportoletti, Lucrecia Yáñez San Segundo, Alicia Enrico, Elżbieta Kalicińska, Ewa Wasik-Szczepanek, Martin Spacek, Tamar Tadmor, Enrico Lista, Roel van Kampen, Lorella Orsucci, Michael Doubek, Yair Herishanu, Blanca Espinet, Jose Angel Hernandez-Rivas, Inga Piskunova, Ozren Jakšić, Georgios Karakatsoulis, Tomasz Wróbel, Oana Stanca, Luca Laurenti, Martin Andres, Roberto Marasca, Mark-David Levin, Giovanni Del Poeta, Miguel Arturo Pavlovsky, Maria Dimou, Monia Marchetti, Ivana Milosevic, Gianluigi Reda, Tobias Herold, David Allsup, Raul Cordoba, Andrea Visentin, Maria Gomes da Silva, Angela Ferrari, Antonella Capasso, Juan Marquet, Francesca Maria Quaglia, Candida Vitale, Mattias Mattsson, Marta Coscia, Moritz Fürstenau, Lucia Farina, Niki Stavroyianni, Marta Morawska, Arnon P. Kater, Mónica Baile, Gevorg Saghumyan, Carolina Cuéllar-García, Jacopo Olivieri, Darko Antic, Raquel Nunes Rodrigues, Alejandro Alonso Cabrero, Henrik Frederiksen, Alessandro Rambaldi, Marzia Varettoni, Amit Shrestha, Оlga B Kalashnikova, Thomas Chatzikonstantinou, José A. García-Marco, Martin Simkovic, Linda Katharina Karlsson, Odit Gutwein, Mohamed A. Yassin, Rosa Ruchlemer, Eva Gimeno, Kristian Qvist, Fatima Miras, Gilad Itchaki, Maria Rosaria De Paolis, Maria Efstathopoulou, Doreen te Raa, Barbara Eichhorst, Dominique Bron, Jorge Labrador, Gian Matteo Rigolin, Myriam Foglietta, Massimo Gentile, Sofia Chatzileontiadou, Carsten Utoft Niemann, Anargyros Kapetanakis, Kostas Stamatopoulos, Lorenzo De Paoli, Giulia Quaresmini, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Interne Geneeskunde, MUMC+: MA Hematologie (9), Chatzikonstantinou, T., Kapetanakis, A., Scarfo, L., Karakatsoulis, G., Allsup, D., Cabrero, A. A., Andres, M., Antic, D., Baile, M., Baliakas, P., Bron, D., Capasso, A., Chatzileontiadou, S., Cordoba, R., Correa, J. -G., Cuellar-Garcia, C., De Paoli, L., De Paolis, M. R., Del Poeta, G., Demosthenous, C., Dimou, M., Donaldson, D., Doubek, M., Efstathopoulou, M., Eichhorst, B., El-Ashwah, S., Enrico, A., Espinet, B., Farina, L., Ferrari, A., Foglietta, M., Frederiksen, H., Furstenau, M., Garcia-Marco, J. A., Garcia-Serra, R., Gentile, M., Gimeno, E., Glenthoj, A., Gomes da Silva, M., Gutwein, O., Hakobyan, Y. K., Herishanu, Y., Hernandez-Rivas, J. A., Herold, T., Innocenti, I., Itchaki, G., Jaksic, O., Janssens, A., Kalashnikova, Оb., Kalicinska, E., Karlsson, L. K., Kater, A. P., Kersting, S., Labrador, J., Lad, D., Laurenti, L., Levin, M. -D., Lista, E., Lopez-Garcia, A., Malerba, L., Marasca, R., Marchetti, M., Marquet, J., Mattsson, M., Mauro, F. R., Milosevic, I., Miras, F., Morawska, M., Motta, M., Munir, T., Murru, R., Niemann, C. U., Rodrigues, R. N., Olivieri, J., Orsucci, L., Papaioannou, M., Pavlovsky, M. A., Piskunova, I., Popov, V. M., Quaglia, F. M., Quaresmini, G., Qvist, K., Reda, G., Rigolin, G. M., Ruchlemer, R., Saghumyan, G., Shrestha, A., Simkovic, M., Spacek, M., Sportoletti, P., Stanca, O., Stavroyianni, N., Tadmor, T., Te Raa, D., Tonino, S. H., Trentin, L., Van Der Spek, E., van Gelder, M., van Kampen, R., Varettoni, M., Visentin, A., Vitale, C., Wasik-Szczepanek, E., Wrobel, T., San Segundo, L. Y., Yassin, M., Coscia, M., Rambaldi, A., Montserrat, E., Foa, R., Cuneo, A., Stamatopoulos, K., Ghia, P., Experimental Immunology, Clinical Haematology, AII - Cancer immunology, and CCA - Cancer Treatment and Quality of Life
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Chronic lymphocytic leukaemia ,Cancer Research ,medicine.medical_specialty ,COVID-19 Vaccines ,Coronavirus disease 2019 (COVID-19) ,Epidemiology ,medicine.medical_treatment ,Chronic lymphocytic leukemia ,CLL, COVID-19 ,610 Medicine & health ,Disease ,Lower risk ,COVID-19 (Malaltia) ,Severity of Illness Index ,Article ,NO ,law.invention ,Risk Factors ,law ,Internal medicine ,Case fatality rate ,Mortalitat ,medicine ,Humans ,Hematologi ,Chronic ,Mortality ,Science & Technology ,Leukemia ,SARS-CoV-2 ,business.industry ,Vaccination ,B-Cell ,Leucèmia ,COVID-19 ,Immunosuppression ,Hematology ,Prognosis ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Survival Analysis ,Intensive care unit ,Lymphocytic ,Oncology ,business ,Life Sciences & Biomedicine - Abstract
Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p
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- 2021
25. What did you do to stay ‘sane’ during the pandemic? A qualitative study to identify self-care mental health strategies utilized in a socially vulnerable population
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Ronald Fischer, Beatriz Bozza, Carolina Victorino, Marina Motta, Luna Arouca, and Fernando A. Bozza
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Immunology and Microbiology (miscellaneous) ,Health Policy ,Public Health, Environmental and Occupational Health ,Medicine (miscellaneous) ,Biochemistry, Genetics and Molecular Biology (miscellaneous) - Abstract
BackgroundMental health has deteriorated during the COVID-19 pandemic. These impacts are likely to be more severe in socially vulnerable communities. Previous research has identified useful self-help strategies that individuals may use to maintain and improve mental health. However, these studies have typically ignored economically and socially marginalized communities and have used researcher pre-defined practices. Little is known what activities or actions members of poor urban communities from low and middle income countries may utilize to take care of their mental health. MethodsDuring March and April 2021, we conducted open-ended interviews with 317 community members in Complexo de Favelas da Maré, Rio de Janeiro, Brazil, one of the largest slum areas in South America. Individuals were interviewed in selected public spaces to provide a representative sample of the wider area. Our sample consisted of 178 (56.1%) cis women, 133 (41.9%) cis men, 3 (0.9%) trans men, and 3 (0.9%) classified themselves as other. The majority of participants had incomplete middle school or less (54.2%) and were between 30 and 60 years (54.1%). ResultsUsing thematic analysis, we identified eight major themes in the responses. The most common themes that emerged were work, leisure activities (including watching TV & physical exercise) and religion/prayer. These findings did not clearly align with previous mental health recommendations. Some results were noteworthy by their absence, e.g., cost-effective mental health practices such as yoga, meditation or mindfulness were not mentioned. Only 4 individuals reported consulting mental health professionals during the pandemic. ConclusionsOur findings highlight the need for better public health campaigns that disseminate information for effective mental health practices during acute crises, especially for communities that are most vulnerable during public health crises.
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- 2022
26. Author response for 'Management of chronic lymphocytic leukemia in Italy during a one year of the COVID‐19 pandemic and at the start of the vaccination program. A Campus CLL report'
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null Antonio Cuneo, null Gian Matteo Rigolin, null Marta Coscia, null Giulia Quaresmini, null Lydia Scarfò, null Francesca Romana Mauro, null Marina Motta, null Francesca Maria Quaglia, null Livio Trentin, null Andrea Ferrario, null Luca Laurenti, null Gianluigi Reda, null Angela Ferrari, null Daniela Pietrasanta, null Paolo Sportoletti, null Francesca Re, null Lorenzo De Paoli, null Myriam Foglietta, null Annamaria Giordano, null Monia Marchetti, null Lucia Farina, null Giovanni Del Poeta, null Marzia Varettoni, null Federico Chiurazzi, null Roberto Marasca, null Lara Malerba, null Adalberto Ibatici, null Maria Chiara Tisi, null Vittorio Stefoni, null Monica Leone, null Claudia Baratè, null Jacopo Olivieri, null Roberta Murru, null Massimo Gentile, null Alessandro Sanna, null Alessandro Gozzetti, null Valter Gattei, null Daniela Gottardi, null Enrico Derenzini, null Luciano Levato, null Lorella Orsucci, null Giuseppa Penna, null Annalisa Chiarenza, and null Robin Foà
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- 2021
27. MOLTO, A MULTICENTER, OPEN LABEL, UNCONTROLLED, PHASE II CLINICAL TRIAL ON VENETOCLAX, ATEZOLIZUMAB, OBINUTUZUMAB IN RICHTER TRANSFORMATION: SAFETY INTERIM ANALYSIS
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Marina Motta, Anna Maria Frustaci, Alessandra Tedeschi, Marina Deodato, D. Rossi, P. L. Zinzani, Gianluca Gaidano, Marco Montillo, Roberto Cairoli, Marta Coscia, Giulia Zamprogna, Candida Vitale, Daniela Pietrasanta, Thorsten Zenz, and Lydia Scarfò
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Oncology ,Cancer Research ,medicine.medical_specialty ,Richter transformation ,business.industry ,Venetoclax ,Hematology ,General Medicine ,Interim analysis ,Clinical trial ,chemistry.chemical_compound ,chemistry ,Obinutuzumab ,Atezolizumab ,Internal medicine ,Medicine ,Open label ,business - Published
- 2021
28. DIRECT‐ACTING ANTIVIRALS AS PRIMARY TREATMENT FOR HCV‐ASSOCIATED INDOLENT NON‐HODGKIN LYMPHOMAS: THE PROSPECTIVE BART STUDY OF THE FONDAZIONE ITALIANA LINFOMI
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Carlo Visco, Lorella Orsucci, Daniele Vallisa, Marco Paulli, Luigi Marcheselli, Sara Rattotti, Raffaele Bruno, Anna Dodero, Anna Linda Zignego, Antonella Santoro, Omar Perbellini, Andrés J.M. Ferreri, Michele Spina, Francesca Re, Valentina Zuccaro, Stefano Luminari, Marina Motta, Alessandro Pulsoni, Emanuela Chimienti, Luca Arcaini, Michele Merli, Francesco Russo, and Francesco Piazza
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Primary treatment ,Hematology ,General Medicine ,business ,DIRECT ACTING ANTIVIRALS - Published
- 2021
29. Management of chronic lymphocytic leukemia in Italy during a one year of the COVID-19 pandemic and at the start of the vaccination program. A Campus CLL report
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Marina Motta, Daniela Gottardi, Vittorio Stefoni, Daniela Pietrasanta, Gianluigi Reda, Lydia Scarfò, Gian Matteo Rigolin, Annalisa Chiarenza, Francesca Maria Quaglia, Maria Chiara Tisi, Alessandro Sanna, Luciano Levato, Robin Foà, Monica Leone, Livio Trentin, Massimo Gentile, Monia Marchetti, Adalberto Ibatici, Enrico Derenzini, Roberta Murru, Antonio Cuneo, Angela Ferrari, Giulia Quaresmini, Francesca Romana Mauro, Annamaria Giordano, Lucia Farina, Myriam Foglietta, Paolo Sportoletti, Lara Malerba, Alessandro Gozzetti, Roberto Marasca, Federico Chiurazzi, Lorenzo De Paoli, Francesca Re, Giovanni Del Poeta, Andrea Ferrario, Marta Coscia, Luca Laurenti, Lorella Orsucci, Marzia Varettoni, Claudia Baratè, Giuseppa Penna, Valter Gattei, Jacopo Olivieri, Cuneo, A., Rigolin, G. M., Coscia, M., Quaresmini, G., Scarfo', L., Mauro, F. R., Motta, M., Quaglia, F. M., Trentin, L., Ferrario, A., Laurenti, L., Reda, G., Ferrari, A., Pietrasanta, D., Sportoletti, P., Re, F., De Paoli, L., Foglietta, M., Giordano, A., Marchetti, M., Farina, L., Del Poeta, G., Varettoni, M., Chiurazzi, F., Marasca, R., Malerba, L., Ibatici, A., Tisi, M. C., Stefoni, V., Leone, M., Barate, C., Olivieri, J., Murru, R., Gentile, M., Sanna, A., Gozzetti, A., Gattei, V., Gottardi, D., Derenzini, E., Levato, L., Orsucci, L., Penna, G., Chiarenza, A., and Foa, R.
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Male ,Cancer Research ,2019-20 coronavirus outbreak ,Time Factors ,targeted agents ,Coronavirus disease 2019 (COVID-19) ,Chronic lymphocytic leukemia ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,NO ,COVID‐19 ,Pandemic ,medicine ,Humans ,Chronic ,chronic lymphocytic leukemia ,COVID-19 ,vaccination ,Letter to the Editor ,Aged ,Leukemia ,business.industry ,SARS-CoV-2 ,Vaccination ,B-Cell ,Disease Management ,Hematology ,General Medicine ,Middle Aged ,medicine.disease ,Prognosis ,Virology ,Leukemia, Lymphocytic, Chronic, B-Cell ,Lymphocytic ,Settore MED/15 - MALATTIE DEL SANGUE ,Oncology ,Italy ,Female ,business - Published
- 2021
30. Clinical characteristics and risk factors for mortality in hematologic patients affected by COVID‐19
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Angelo Belotti, Mariella D'Adda, Chiara Pagani, Erika Borlenghi, Kordelia Barbullushi, Daniela Dalceggio, Alessandro Re, Annalisa Peli, Aldo M. Roccaro, Nicola Bianchetti, Rosa Daffini, Massimo Salvetti, Giuseppe Rossi, Maria Lorenza Muiesan, Alessandra Tucci, Valeria Cancelli, Margherita Oberti, Anna Paini, Valentina Mancini, Roberto Cairoli, Chiara Cattaneo, Carolina De Ciuceis, Antonella Anastasia, Marina Motta, Cattaneo, C, Daffini, R, Pagani, C, Salvetti, M, Mancini, V, Borlenghi, E, D'Adda, M, Oberti, M, Paini, A, De Ciuceis, C, Barbullushi, K, Cancelli, V, Belotti, A, Re, A, Motta, M, Peli, A, Bianchetti, N, Anastasia, A, Dalceggio, D, Roccaro, A, Tucci, A, Cairoli, R, Muiesan, M, and Rossi, G
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Male ,medicine.medical_specialty ,Cancer Research ,Anemia ,Pneumonia, Viral ,Population ,Disease ,Betacoronavirus ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Correspondence ,Epidemiology ,medicine ,Humans ,risk factors ,030212 general & internal medicine ,education ,Pandemics ,Aged ,Retrospective Studies ,coronavirus disease 2019 (COVID-19) ,epidemiology ,hematologic patients ,outcome ,education.field_of_study ,SARS-CoV-2 ,business.industry ,Mortality rate ,COVID-19 ,Respiratory infection ,Cancer ,Prognosis ,medicine.disease ,Survival Rate ,Italy ,Hematologic disease ,risk factor ,Oncology ,Hematologic Neoplasms ,030220 oncology & carcinogenesis ,hematologic patient ,Female ,Coronavirus Infections ,business ,Follow-Up Studies - Abstract
Background: Patients with cancer are considered highly vulnerable to the recent coronavirus disease 2019 (COVID-19) pandemic. However, there are still few data on COVID-19 occurring in hematologic patients. Methods: One hundred two patients with COVID-19 symptoms and a nasopharyngeal swab positive for severe acute respiratory syndrome coronavirus 2 seen at 2 hematologic departments located in Lombardy, Italy, during March 2020 were studied. Risk factors for acquiring COVID-19 were analyzed by comparisons of patients with COVID-19 and the standard hematologic population managed at the same institutions in 2019. Thirty-day survival was compared with the survival of matched uninfected control patients with similar hematologic disorders and nonhematologic patients affected by COVID-19. Results: Male sex was significantly more prevalent in patients with COVID-19. The infection occurred across all different types of hematologic disease; however, the risk of acquiring a COVID-19 infection was lower for patients with chronic myeloproliferative neoplasms, including chronic myeloid leukemia, and higher for patients with immune-mediated anemia on immunosuppressive-related treatments. The 30-day mortality rate was 39.2%, which was higher than the rates for nonhematologic patients with COVID-19 (23.5%; P =.02) and uninfected hematologic controls (3%; P
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- 2020
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31. Zanubrutinib for the treatment of MYD88 wild-type Waldenström macroglobulinemia: a substudy of the phase 3 ASPEN trial
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Marek Trneny, Aileen Cohen, Elham Askari, Judith Trotman, Sebastian Grosicki, Ziwen Tan, Jingjing Schneider, Ramón García Sanz, Marzia Varettoni, Hui-Peng Lee, Jane Huang, Jan Michel, Constantine S. Tam, Christian Buske, Pier Luigi Zinzani, Jorge J. Castillo, Marina Motta, Albert Oriol, Tanya Siddiqi, Roger G. Owen, Simon Rule, Alessandra Tedeschi, Veronique Leblond, Wai Y. Chan, Mercedes Gironella Mesa, Stephen P. Mulligan, Jarosław Czyż, Meletios A. Dimopoulos, Gavin Cull, Stephen Opat, Janusz Kloczko, Dipti Talaulikar, Shirley D'Sa, Miquel Granell Gorrochategui, Dimopoulos M., Sanz R.G., Lee H.-P., Trneny M., Varettoni M., Opat S., D'Sa S., Owen R.G., Cull G., Mulligan S., Czyz J., Castillo J.J., Motta M., Siddiqi T., Mesa M.G., Gorrochategui M.G., Talaulikar D., Zinzani P.L., Askari E., Grosicki S., Oriol A., Rule S., Kloczko J., Tedeschi A., Buske C., Leblond V., Trotman J., Chan W.Y., Michel J., Schneider J., Tan Z., Cohen A., Huang J., and Tam C.S.
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0301 basic medicine ,Oncology ,Bendamustine ,medicine.medical_specialty ,Clinical Trials and Observations ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,Piperidines ,law ,Internal medicine ,medicine ,Bruton's tyrosine kinase ,Humans ,Adverse effect ,biology ,business.industry ,Waldenstrom macroglobulinemia ,Hematology ,medicine.disease ,Clinical trial ,030104 developmental biology ,Pyrimidines ,chemistry ,030220 oncology & carcinogenesis ,Ibrutinib ,Cohort ,Myeloid Differentiation Factor 88 ,biology.protein ,Pyrazoles ,Waldenstrom Macroglobulinemia ,business ,medicine.drug ,Waldenström macroglobulinemia, MYD88 gene mutations, Zanubrutinib, Bruton tyrosine kinase inhibitor - Abstract
Patients with Waldenström macroglobulinemia (WM) lacking activating mutations in the MYD88 gene (MYD88WT) have demonstrated relatively poor outcomes to ibrutinib monotherapy, with no major responses reported in a phase 2 pivotal study. Zanubrutinib is a novel, selective Bruton tyrosine kinase (BTK) inhibitor designed to maximize BTK occupancy and minimize off-target activity. The ASPEN study consisted of a randomized comparison of zanubrutinib and ibrutinib efficacy and safety in patients with WM who have the MYD88 mutation, as well as a separate cohort of patients without MYD88 mutation (MYD88WT) or with unknown mutational status who received zanubrutinib. Results from the latter single-arm cohort are reported herein. Efficacy endpoints included overall, major and complete (CR) or very good partial response (VGPR) rates, progression-free survival (PFS), duration of response (DOR), and overall survival (OS). Twenty-eight patients (23 relapsed/refractory; 5 treatment-naïve) were enrolled, including 26 with centrally confirmed MYD88WT disease and 2 with unknown MYD88 mutational status. At a median follow-up of 17.9 months, 7 of 26 MYD88WT patients (27%) had achieved a VGPR and 50% a major response (partial response or better); there were no CRs. At 18 months, the estimated PFS and OS rates were 68% and 88%, respectively, while the median DOR had not been reached. Two patients discontinued zanubrutinib due to adverse events. Treatment-emergent hypertension, atrial fibrillation, and major hemorrhages were reported in 3, 1 and 2 patients (including 1 concurrent with enoxaparin therapy), respectively. Results of this substudy demonstrate that zanubrutinib monotherapy can induce high quality responses in patients with MYD88WT WM. This trial is registered on www.clinicaltrials.gov as NCT #03053440.
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- 2020
32. A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström macroglobulinemia: the ASPEN study
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Gavin Cull, Wai Y. Chan, Jorge J. Castillo, Helen McCarthy, Ramón García Sanz, Monique C. Minnema, Wojciech Jurczak, Jarosław Czyż, Edward N. Libby, Hui Peng Lee, Marina Motta, Shirley D'Sa, Monica Tani, Constantine S. Tam, Judith Trotman, Paula Marlton, Stephen Opat, Tanya Siddiqi, Björn E. Wahlin, Roger G. Owen, Christian Buske, Jeffrey Matous, Meletios A. Dimopoulos, Marek Trneny, David Belada, Jingjing Schneider, Carlos Fernández de Larrea, Jane Huang, Alessandra Tedeschi, Veronique Leblond, Stephen P. Mulligan, Aileen Cohen, and Sunhee Ro
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Adult ,Male ,medicine.medical_specialty ,Clinical Trials and Observations ,Immunology ,Peripheral edema ,Neutropenia ,Biochemistry ,Gastroenterology ,Cohort Studies ,chemistry.chemical_compound ,Piperidines ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Clinical endpoint ,Humans ,Adverse effect ,Survival rate ,Aged ,Aged, 80 and over ,business.industry ,Adenine ,Waldenstrom macroglobulinemia ,Cell Biology ,Hematology ,Middle Aged ,medicine.disease ,Prognosis ,Discontinuation ,Survival Rate ,Pyrimidines ,chemistry ,Ibrutinib ,Pyrazoles ,Female ,medicine.symptom ,Waldenstrom Macroglobulinemia ,business ,Follow-Up Studies - Abstract
Bruton tyrosine kinase (BTK) inhibition is an effective treatment approach for patients with Waldenström macroglobulinemia (WM). The phase 3 ASPEN study compared the efficacy and safety of ibrutinib, a first-generation BTK inhibitor, with zanubrutinib, a novel highly selective BTK inhibitor, in patients with WM. Patients with MYD88L265P disease were randomly assigned 1:1 to treatment with ibrutinib or zanubrutinib. The primary end point was the proportion of patients achieving a complete response (CR) or a very good partial response (VGPR) by independent review. Key secondary end points included major response rate (MRR), progression-free survival (PFS), duration of response (DOR), disease burden, and safety. A total of 201 patients were randomized, and 199 received ≥1 dose of study treatment. No patient achieved a CR. Twenty-nine (28%) zanubrutinib patients and 19 (19%) ibrutinib patients achieved a VGPR, a nonstatistically significant difference (P = .09). MRRs were 77% and 78%, respectively. Median DOR and PFS were not reached; 84% and 85% of ibrutinib and zanubrutinib patients were progression free at 18 months. Atrial fibrillation, contusion, diarrhea, peripheral edema, hemorrhage, muscle spasms, and pneumonia, as well as adverse events leading to treatment discontinuation, were less common among zanubrutinib recipients. Incidence of neutropenia was higher with zanubrutinib, although grade ≥3 infection rates were similar in both arms (1.2 and 1.1 events per 100 person-months). These results demonstrate that zanubrutinib and ibrutinib are highly effective in the treatment of WM, but zanubrutinib treatment was associated with a trend toward better response quality and less toxicity, particularly cardiovascular toxicity.
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- 2020
33. COVID-19 severity and mortality in patients with chronic lymphocytic leukemia: a joint study by ERIC, the European Research Initiative on CLL, and CLL Campus
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Tobias Herold, Martin Andres, Gimena Dos Santos, Livio Trentin, Monia Marchetti, Antonio Cuneo, Robin Foà, Vladimir Strugov, Sunil Iyengar, Ozren Jakšić, Mark-David Levin, Angela Ferrari, Francesca Romana Mauro, Candida Vitale, Martin Spacek, Olga Kalashnikova, Eugene Nikitin, Ann Janssens, Constantine S. Tam, Julio Delgado, Maria Papaioannou, Barbara Pocali, Davide Rossi, Marina Motta, Niki Stavroyianni, Myriam Foglietta, Alicia Enrico, Carolina Cuéllar-García, Lara Malerba, Mónica Baile, Lydia Scarfò, Ellen van der Spek, Paolo Sportoletti, Maria Rosaria De Paolis, Mihnea Zdrenghea, Macarena Ortiz Pareja, Annalisa Chiarenza, Sabina Kersting, Fatima Miras, Yair Herishanu, Emili Montserrat, Marta Coscia, Giuseppe Rossi, Jose Angel Hernandez-Rivas, Carsten Utoft Niemann, Alessandro Rambaldi, Amit Shrestha, Roberto Marasca, Rosa Ruchlemer, Marzia Varettoni, Dominique Bron, Juan Marquet, Eva Gimeno, Viola Maria Popov, Massimo Gentile, Mohamed A. Yassin, Kostas Stamatopoulos, Lorenzo De Paoli, Thomas Chatzikonstantinou, Giulia Quaresmini, Luca Laurenti, Lucia Farina, Arnon P. Kater, Nimish Shah, Elisabeth Vandenberghe, José A. García-Marco, Oana Stanca, Giovanni Del Poeta, Martin Simkovic, Yervand K Hakobyan, Enrico Lista, Michael Doubek, Gilad Itchaki, Talha Munir, Paolo Ghia, Ewa Wasik-Szczepanek, Gianluigi Reda, Francesca Maria Quaglia, Maria Dimou, Gábor Barna, Lorella Orsucci, Gian Matteo Rigolin, Scarfo', L., Chatzikonstantinou, T., Rigolin, G. M., Quaresmini, G., Motta, M., Vitale, C., Garcia-Marco, J. A., Hernandez-Rivas, J. A., Miras, F., Baile, M., Marquet, J., Niemann, C. U., Reda, G., Munir, T., Gimeno, E., Marchetti, M., Quaglia, F. M., Varettoni, M., Delgado, J., Iyengar, S., Janssens, A., Marasca, R., Ferrari, A., Cuellar-Garcia, C., Itchaki, G., Spacek, M., De Paoli, L., Laurenti, L., Levin, M. -D., Lista, E., Mauro, F. R., Simkovic, M., Van Der Spek, E., Vandenberghe, E., Trentin, L., Wasik-Szczepanek, E., Ruchlemer, R., Bron, D., De Paolis, M. R., Del Poeta, G., Farina, L., Foglietta, M., Gentile, M., Herishanu, Y., Herold, T., Jaksic, O., Kater, A. P., Kersting, S., Malerba, L., Orsucci, L., Popov, V. M., Sportoletti, P., Yassin, M., Pocali, B., Barna, G., Chiarenza, A., dos Santos, G., Nikitin, E., Andres, M., Dimou, M., Doubek, M., Enrico, A., Hakobyan, Y., Kalashnikova, O., Ortiz Pareja, M., Papaioannou, M., Rossi, D., Shah, N., Shrestha, A., Stanca, O., Stavroyianni, N., Strugov, V., Tam, C., Zdrenghea, M., Coscia, M., Stamatopoulos, K., Rossi, G., Rambaldi, A., Montserrat, E., Foa, R., Cuneo, A., Ghia, P., Experimental Immunology, Clinical Haematology, and CCA - Cancer Treatment and Quality of Life
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0301 basic medicine ,Male ,Chronic lymphocytic leukaemia ,Cancer Research ,Chronic Lymphocytic Leukemia, COVID-19 ,Chronic lymphocytic leukemia ,Comorbidity ,Severity of Illness Index ,chemistry.chemical_compound ,0302 clinical medicine ,Piperidines ,Obinutuzumab ,Surveys and Questionnaires ,hemic and lymphatic diseases ,80 and over ,Viral ,Chronic ,610 Medicine & health ,Immunodeficiency ,Aged, 80 and over ,Leukemia ,Mortality rate ,Age Factors ,Hematology ,Middle Aged ,Prognosis ,Lymphocytic ,Oncology ,030220 oncology & carcinogenesis ,Infectious diseases ,Female ,Coronavirus Infections ,medicine.drug ,Bendamustine ,medicine.medical_specialty ,Pneumonia, Viral ,Antineoplastic Agents ,Article ,NO ,03 medical and health sciences ,Betacoronavirus ,Internal medicine ,Severity of illness ,medicine ,Humans ,Chronic Lymphocytic Leukemia ,Pandemics ,Protein Kinase Inhibitors ,Aged ,Retrospective Studies ,SARS-CoV-2 ,Venetoclax ,business.industry ,Adenine ,B-Cell ,COVID-19 ,Odds ratio ,Pneumonia ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Settore MED/15 - MALATTIE DEL SANGUE ,030104 developmental biology ,Pyrazoles ,Pyrimidines ,chemistry ,business - Abstract
Chronic lymphocytic leukemia (CLL) is a disease of the elderly, characterized by immunodeficiency. Hence, patients with CLL might be considered more susceptible to severe complications from COVID-19. We undertook this retrospective international multicenter study to characterize the course of COVID-19 in patients with CLL and identify potential predictors of outcome. Of 190 patients with CLL and confirmed COVID-19 diagnosed between 28/03/2020 and 22/05/2020, 151 (79%) presented with severe COVID-19 (need of oxygen and/or intensive care admission). Severe COVID-19 was associated with more advanced age (≥65 years) (odds ratio 3.72 [95% CI 1.79–7.71]). Only 60 patients (39.7%) with severe COVID-19 were receiving or had recent (≤12 months) treatment for CLL at the time of COVID-19 versus 30/39 (76.9%) patients with mild disease. Hospitalization rate for severe COVID-19 was lower (p < 0.05) for patients on ibrutinib versus those on other regimens or off treatment. Of 151 patients with severe disease, 55 (36.4%) succumbed versus only 1/38 (2.6%) with mild disease; age and comorbidities did not impact on mortality. In CLL, (1) COVID-19 severity increases with age; (2) antileukemic treatment (particularly BTK inhibitors) appears to exert a protective effect; (3) age and comorbidities did not impact on mortality, alluding to a relevant role of CLL and immunodeficiency.
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- 2020
34. Younger patients with Waldenström Macroglobulinemia exhibit low risk profile and excellent outcomes in the era of immunotherapy and targeted therapies
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Angela Ferrari, Carlo Visco, Rita Rizzi, Andrea Corbingi, Anna Maria Frustaci, Luca Laurenti, Marzia Varettoni, Corinna Greco, Stefano Luminari, Michele Merli, Antonio Abbadessa, Vittorio Del Fabro, Luca Arcaini, Giulia Benevolo, Virginia Valeria Ferretti, Massimo Gentile, Francesco Piazza, Marina Deodato, Irene Dogliotti, Catherine Klersy, Marina Motta, Pellegrino Musto, Simone Ferrero, and Nicole Fabbri
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Adult ,Male ,medicine.medical_specialty ,Population ,Asymptomatic ,Disease-Free Survival ,Autologous stem-cell transplantation ,Piperidines ,Risk Factors ,Internal medicine ,Age Factors ,Autografts ,Female ,Humans ,Middle Aged ,Pyrazoles ,Pyrimidines ,Survival Rate ,Immunotherapy ,Stem Cell Transplantation ,Waldenstrom Macroglobulinemia ,medicine ,WM ,Risk factor ,education ,Survival rate ,education.field_of_study ,business.industry ,Adenine ,Waldenstrom macroglobulinemia ,Retrospective cohort study ,Hematology ,medicine.disease ,Settore MED/15 - MALATTIE DEL SANGUE ,medicine.symptom ,business ,Cohort study - Abstract
We analyzed 160 young Waldenström Macroglobulinemia (WM) patients with a median age of 49 years (range 23-55 years), diagnosed between January 2000 and January 2019 in 14 Italian centers. At diagnosis, 70% of patients were asymptomatic. With a median follow-up of 5.6 years, 57% have been treated. As initial therapy 79% of patients received chemo-immunotherapy, 13% a chemo-free induction and 8% chemotherapy only. At relapse or progression, 6% underwent an autologous stem cell transplantation. Overall, 19% of patients received ibrutinib during the course of the disease. According to IPSSWM, 63% were classified as low risk, 27% as intermediate risk and 10% as high risk. Five-year OS was shorter in high-risk as compared with low or intermediate risk patients (92.9% vs 100% P = .002). According to revised IPSSWM, 92% were classified as very low or low risk and 8% as intermediate risk, with a shorter 5-year OS in the latter group (87.5% vs 100%, P = .028). The OS of young WM patients was not significantly reduced as compared with age-matched, sex-matched and calendar year-matched general population. Early diagnosis, absence of high-risk features in symptomatic patients and high efficacy of modern treatments are the main determinants of the excellent outcome of young WM patients.
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- 2020
35. P059 Corticosteroids, Aminosalicylates and Gastrointestinal Symptoms Are Associated With the Need of Hospitalization in Patients With Inflammatory Bowel Diseases and COVID-19
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Marcela, Vasconcellos, primary, Marina, Motta, additional, Caio, Freire, additional, Fabio, Teixeira, additional, Liliana, Chebli, additional, Rogerio, Saad-Hossne, additional, and Natália, Queiroz, additional
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- 2020
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36. P063 Manometric Study and the Role of the Perianal Disease and the Clinical Activity in Anorectal Dysfunction in Crohn's Disease
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Lina, Codes, primary, Ana, Jesus, additional, Reginaldo, Ferreira, additional, Carolina, Sacramento, additional, Flávia, Fidelis, additional, Isabela, Cruz, additional, Marina, Motta, additional, Cândida, Alves, additional, Aline, Trajano, additional, Viviane, Gusmão, additional, João, Codes, additional, and Genoile, Santana, additional
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- 2020
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37. Minimal Residual Disease-Driven Treatment Intensification By Sequential Addition of Ibrutinib to Venetoclax in Relapsed/Refractory Chronic Lymphocytic Leukemia: Results of the Monotherapy and Combination Phases of the Improve Study
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Pamela Ranghetti, Elisa Albi, Maria Colia, Eloise Scarano, Paolo Ghia, Andrea Ferrario, Marco Ladetto, Antonella Capasso, Silvia Heltai, Luana Schiattone, Rosaria Sancetta, Luca Laurenti, Marzia Varettoni, Lydia Scarfò, Marina Deodato, Eleonora Perotta, Gianluca Gaidano, Gianluigi Reda, Marina Motta, Marta Coscia, and Lucia Farina
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medicine.medical_specialty ,business.industry ,Venetoclax ,Treatment intensification ,Immunology ,Cell Biology ,Hematology ,Biochemistry ,Minimal residual disease ,Discontinuation ,chemistry.chemical_compound ,chemistry ,Internal medicine ,Ibrutinib ,Relapsed refractory ,Ven ,Clinical endpoint ,Medicine ,business - Abstract
The treatment of chronic lymphocytic leukemia (CLL) has been radically changed in the last years thanks to the targeted therapies, including kinase (i.e. ibrutinib) and BCL2 (i.e. venetoclax) inhibitors. Venetoclax (VEN) in particular is able to obtain undetectable minimal residual disease (uMRD), though only in a proportion of patients (pts) when given as single agent, thus warranting the need of different strategies in those not achieving uMRD. We designed a phase 2 multicenter Italian study where ibrutinib (IBR) is added to VEN based on a MRD-driven strategy aiming at obtaining uMRD and discontinuing both treatments in pts who did not achieve uMRD with VEN mono. Study treatment started with VEN (ramp up to 400 mg/day as per current label) for 12 months. MRD status in peripheral blood (PB) and bone marrow (BM) was evaluated using the 6-color flow cytometry assay recommended by ERIC (CD5/CD81/CD79b/CD19/CD43/CD20). Pts with uMRD in both PB and BM at C12D1 discontinued VEN at C12D28 and entered the follow-up phase. Pts with detectable MRD in PB and/or BM added IBR 420 mg/day starting from C13D1 and continued both drugs up to maximum C24D28, uMRD, progression or unacceptable toxicity (whichever occurs first). After C24D28, pts with detectable MRD and still in response continued IBR alone. The primary endpoint was uMRD4 ( Thirty-eight pts (recruited from Nov 2017 to Jul 2018) fulfilled eligibility and started VEN. Baseline characteristics included: median number of prior therapies 1 (range 1-4) (60.6% previously treated with FCR or FC); del(17p) in 8/33 (24%); TP53 mutations in 10/30 (33%), and unmutated IGHV in 24/30 (80%). At the data cut-off, 35/38 evaluable pts still in the study have reached C24D1, 1 pt discontinued treatment due to myelodisplasia (considered unrelated to study treatment) before C12D1 and 1 pt progressed on VEN monotherapy shortly before that timepoint, 1 evaluation is still missing due to COVID-19 restrictions. At C12D1, uMRD4 in PB was achieved in 19/38 (50%) pts (Figure 1), 17/19 (89.5%) had uMRD4 confirmed in BM. Overall response rate with VEN single-agent was 36/38 (94.7%), 9 CR and 27 PR. As per protocol, the 17 pts (45%) with uMRD4 in PB and BM at C12D1 discontinued VEN at C12D28. Nineteen responsive cases with detectable MRD at C12D1 added IBR to VEN starting from C13D1. The combination of IBR and VEN led to an improved reduction of the depth of MRD in all but 3 pts with 16/19 (84%) achieving uMRD4 in both PB and BM between C16D1 (first MRD assessment after starting IBR) and C24D1, thus stopping both therapies as per protocol. After a median follow-up of 25.4 months (range 6.1-33.5) from treatment initiation, no clinical progression was observed among those discontinuing treatment in uMRD, while MRD4 relapse occurred in 21/33. Median time to MRD4 relapse in those who achieved uMRD at any timepoint and discontinued treatment was 4 months (range 2-13). Twelve pts (6 treated with VEN only) remain uMRD after stopping treatment, with a median observation of 13 months (range 3+-18+) since confirmed uMRD4. Safety data were analyzed in the intention-to-treat cohort (39 pts). No cases of clinical tumor lysis syndrome (TLS) and/or biochemical TLS were reported in the 39 pts exposed to VEN. Adverse events (AEs) were mild, with no treatment discontinuations or dose reductions. Five Serious AEs (Table 1) and 130 AEs (Table 2) occurred in 28 patients, without any SUSARs. All 5 SAEs were deemed unrelated to study drug(s) and 4/5 have resolved without sequelae. In conclusion, we here present the updated results of our study including the combination phase of VEN with IBR. This sequential MRD-guided approach was feasible and led to deeper responses in about 85% of pts not achieving uMRD4 after VEN alone. With this tailored and time-limited strategy 33 out of 38 pts (87%) obtained uMRD4 in PB and BM either after VEN monotherapy or the IBR-VEN combination, indicating we may reach identical depth of response with a personalized intensification and avoid unnecessary drug exposure. Time to clinical progression and response to VEN retreatment in this cohort remain to be established as well as the biological characteristics of those pts with persistent MRD despite the combined treatment. Updated results with further sequential MRD and clinical monitoring after treatment discontinuation will be presented at the meeting. Disclosures Scarfo: Gilead: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Farina:Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Gaidano:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astrazeneca: Membership on an entity's Board of Directors or advisory committees; Sunesys: Membership on an entity's Board of Directors or advisory committees. Reda:Janssen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees. Coscia:Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Karyopharm Therapeutics: Research Funding. Laurenti:Roche: Honoraria; Gilead: Honoraria; Janssen: Honoraria; AbbVie: Honoraria. Varettoni:Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Other: Travel/accommodations/expenses; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel/accommodations/expenses. Ghia:Lilly: Consultancy, Honoraria; Sunesis: Consultancy, Honoraria, Research Funding; Adaptive, Dynamo: Consultancy, Honoraria; MEI: Consultancy, Honoraria; Celgene/Juno: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; BeiGene: Consultancy, Honoraria; Acerta/AstraZeneca: Consultancy, Honoraria; ArQule: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Novartis: Research Funding.
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- 2020
38. Multicenter Long Term Follow-up in Hairy Cell Leukemia Patients Treated with Cladribine: A Thirty-Year Experience
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Alessandro Broccoli, Maria Elena Nizzoli, Sofia Kovalchuk, Ombretta Annibali, Andrea Visentin, Luana Fianchi, Lorella Orsucci, Stefano Volpetti, Annamaria Frustaci, Maria Cantonetti, Massimo Offidani, Maria Lucia De Luca, Marianna Criscuolo, Alessandra Tedeschi, Alessio Maria Edoardo Maraglino, Alfonso Piciocchi, Angelica Spolzino, Sergio Storti, Francesco Marchesi, Pier Luigi Zinzani, Enrico Tiacci, Livio Pagano, Brunangelo Falini, Livio Trentin, Eugenio Galli, Luca Guarnera, Caterina Stelitano, Marina Motta, Elettra Galli, Marzia Varettoni, Alessandro Pulsoni, and Antonella Anastasia
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Oncology ,medicine.medical_specialty ,business.industry ,Long term follow up ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Internal medicine ,medicine ,Hairy cell leukemia ,business ,Cladribine ,medicine.drug - Abstract
Hairy cell leukemia (HCL) is a rare lymphoproliferative disease with specific morphologic and molecular features and excellent prognosis. Although high rate of complete response (CR) has been reported after treatment with purine analogs, expecially cladribine (2CDA), relapse may occur during follow-up. The aim of the study is to review the efficacy, safety, long term remission rate and overall survival (OS) in those patients (pts) that received 2CDA as first line treatment. We retrospectively reviewed data of all HCL pts treated with 2CDA between March 1991 and May 2019 at 18 Italian Hematological centers. Among 553 pts reported, only 513 were evaluable because treated with 2CDA alone. Considering the clinical carachteristics, M/F ratio was 4.5 with a median age of 54 years (range 24-88) and ECOG 0 in 85% of cases. Splenomegaly and presence of circulating hairy cells recorded by morphology were reported in 241 (47%) and 138 (27%) pts, respectively. Thirty-seven (7%) pts presented with an infection. Other comorbidities were cardiovascular in 29 (6%) pts, a previous cancer or diabetes in 27 (5%) each, chronic hepatic disorders in 18 (3%), obstructive pulmonary disease in 16 (3%), chronic kidney disease in 3 (1%). Three hundred-thirty (64%) pts received 2CDA intravenously (253 as daily continuous infusion for 5-7 consecutive days and 77 as weekly infusion for 5-7 consecutive weeks) and 183 (36%) subcutaneously. Response criteria were defined as per recent consensus guidelines (Grever MR et al. Blood 2017). The overall response rate (ORR) was 83%: CR in 335 pts (65%) and partial response (PR) in 96 (19%); 40 (8%) pts obtained hematological improvement (HI) and in 42 (8%) no response was observed. Nine of 11 (82%) pts with HI and 18/25 (72%) non responders who received salvage therapy obtained a major response (fig. 1). A slightly higher hemoglobin value (12.4 vs 11.4 g/dl, p=0.044), a reduced frequency of circulating hairy cells (28.7% vs 31.8%, p=0.039), absence of palpable splenomegaly (p= 2CDA is greatly effective in treating HCL, with an ORR of 83%. Early and long term adverse events were rare and easily managed: although HCL-related mortality is still possible, OS at 15 years is higher than 80% Disclosures Motta: Roche: Honoraria; Janssen: Honoraria. Offidani:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; BMS: Consultancy, Honoraria. Tedeschi:Abbvie: Honoraria, Speakers Bureau; Sunesis: Honoraria, Speakers Bureau; Acerta: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Beigene: Honoraria, Speakers Bureau. Trentin:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Octapharma: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Shire: Honoraria. Varettoni:Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Other: Travel/accommodations/expenses; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel/accommodations/expenses. Visentin:Janssen: Honoraria; Gilead: Honoraria; Abbvie: Honoraria. Falini:Roche: Research Funding. Pulsoni:Sandoz: Consultancy; Pfizer: Consultancy; Takeda: Consultancy; Gilead: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau; roche: Consultancy, Speakers Bureau; Merk: Consultancy. Tiacci:Roche: Research Funding; Abbvie: Other: Travel and meeting expenses. Zinzani:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kirin Kyowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics, Inc.: Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Consultancy, Speakers Bureau; Kyowa Kirin: Consultancy, Speakers Bureau; Immune Design: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
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- 2020
39. FGF/FGFR Axis-Blockade Leads to Anti-Tumor Activity in Waldenstrom's Macroglobulinemia By Silencing MYD88
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Katia Todoerti, Giuseppe Rossi, Antonella Anastasia, Marco Mor, Cinzia Caprio, Marina Motta, Cinzia Federico, Alessandra Tucci, Riccardo Castelli, Chiara Cattaneo, Roberto Ronca, Nicole Bozza, Antonio Sacco, Marco Presta, Federica Maccarinelli, Aldo M. Roccaro, Arianna Giacomini, Antonino Neri, and Vanessa Favasuli
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Antitumor activity ,business.industry ,Immunology ,Macroglobulinemia ,Cell Biology ,Hematology ,Fibroblast growth factor ,Biochemistry ,Blockade ,Fibroblast growth factor receptor ,Cancer research ,Gene silencing ,Medicine ,business - Abstract
The human fibroblast growth factor/fibroblast growth factor-receptor (FGF/FGFR) axis deregulation is largely involved in supporting the pathogenesis of hematologic malignancies, including Waldenstrom's Macroglobulinemia (WM). Therefore, novel therapeutics designed to specifically target deregulated signaling pathways in WM are required. We investigated the role of FGF/FGFR system blockade in WM by using a pan-FGF trap molecule, NSC12, a small molecule identified using pharmacophore modeling of the interaction of a minimal PTX3-derived FGF-binding pentapeptide with FGF2. By interrogating the transcriptome signature of patients' BM-derived CD19-positive cells (GEO9656, GEO6691), we found a significant enrichment of FGF/FGFR-driven signaling cascades, including PI3K-AKT, MAPK and STAT3 pathways (FDR In addition, the NSC12-dependent inhibition of MYD88 resulted in silencing of the MAPK-ERK signaling cascade, thus leading to NSC12-induced Myc-silencing in WM cells. We next confirmed the efficacy of NSC12 in silencing bone marrow stromal cell (BMSC)-induced FGFR3 phosphorylation; paralleled by inhibition of of pro-survival pathways, including pAKT, the AKT-downstream pGSK3β; p-ERK; and p-STAT3. Functional sequelae of the FGF/FGFR blockade in WM cells were studied, demonstrating inhibition of WM cell growth, induction of apoptosis, enhanced ER stress and initiation of UPR. Of note, anti-WM activity of NSC12 was also documented using primary bone marrow-derived CD19+ cells isolated from patients with WM. In contrast, NSC12 did not show cytotoxicity on PBMC-derived CD19+ cells isolated from healthy donors. The anti-WM activity exerted by NSC12 was confirmed also within the context of the supportive bone marrow milieu, as shown both in vitro and in vivo. BCWM.1, MWCL1 cells were cultured with NSC12 in the presence or absence of primary WM BMSCs: adherence of WM cells to BMSCs triggered a significant increase in the proliferation, which was inhibited by NSC12in a dose-dependent manner (P Overall, our studies are reporting on the use of NSC12, as a novel potential therapeutic strategy to specifically halt the FGF/FGFR axis in WM; and demonstrate how the observed anti-WM activity exerted by NSC12 may be driven, at least in part, by inhibition of MYD88. Disclosures Motta: Roche: Honoraria; Janssen: Honoraria. Rossi:Alexion: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Advisory board; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria; Amgen: Honoraria; Sanofi: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees. Roccaro:Amgen: Other; AstraZeneca: Research Funding; Celgene: Other; Janssen: Other; Italian Association for Cancer Research (AIRC): Research Funding; Transcan2-ERANET: Research Funding; European Hematology Association: Research Funding.
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- 2020
40. The importance of the genomic landscape in Waldenström's Macroglobulinemia for targeted therapeutical interventions
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Aldo M. Roccaro, Antonio Sacco, Antonella Anastasia, Irene M. Ghobrial, Marina Motta, Giuseppe Rossi, Christopher J. Patterson, Loredana Affò, Marco Presta, Stefano Bazzana, Steven P. Treon, Michele Malagola, Adriano Fenotti, Luisa Imberti, and Domenico Russo
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0301 basic medicine ,Oncology ,Functional role ,Receptors, CXCR4 ,medicine.medical_specialty ,Waldenström’s Macrolobulinemia ,genomics ,Bone marrow transplantation ,Waldenström's Macrolobulinemia ,Review ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Exome Sequencing ,medicine ,Humans ,Transcriptome profiling ,Functional studies ,Genetics ,business.industry ,Gene Expression Profiling ,Disease progression ,Medical school ,Macroglobulinemia ,Waldenstrom macroglobulinemia ,Genomics ,medicine.disease ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,030220 oncology & carcinogenesis ,Mutation ,Myeloid Differentiation Factor 88 ,Disease Progression ,Waldenstrom Macroglobulinemia ,business - Abstract
// Antonio Sacco 1 , Adriano Fenotti 2 , Loredana Affo 2 , Stefano Bazzana 3 , Domenico Russo 4 , Marco Presta 5 , Michele Malagola 4 , Antonella Anastasia 6 , Marina Motta 6 , Christopher J. Patterson 7 , Giuseppe Rossi 6 , Luisa Imberti 1 , Steven P. Treon 7 , Irene M. Ghobrial 7 and Aldo M. Roccaro 1 1 ASST Spedali Civili, Coordinamento e Progettazione Ricerca Clinica, CREA Laboratory, Brescia, BS, Italy 2 ASST Spedali Civili, SITRA, Brescia, BS, Italy 3 ASST Spedali Civili, Collegio IPASVI, Brescia, BS, Italy 4 University of Brescia Medical School, Adult Bone Marrow Transplantation Unit, Brescia, BS, Italy 5 University of Brescia Medical School, Dept. of Molecular and Translational Medicine, Brescia, BS, Italy 6 ASST Spedali Civili, Dept. of Hematology, Brescia, BS, Italy 7 Dana-Farber Cancer Institute, Dept. Medical Oncology, Harvard Medical School, Boston, MA, USA Correspondence to: Aldo M. Roccaro, email: // Keywords : Waldenstrom’s Macrolobulinemia, genomics Received : November 17, 2016 Accepted : February 20, 2017 Published : March 11, 2017 Abstract The Literature has recently reported on the importance of genomics in the field of hematologic malignancies, including B-cell lymphoproliferative disorders such as Waldenstrom’s Macrolgobulinemia (WM). Particularly, whole exome sequencing has led to the identification of the MYD88 L265P and CXCR4 C1013G somatic variants in WM, occurring in about 90% and 30% of the patients, respectively. Subsequently, functional studies have demonstrated their functional role in supporting WM pathogenesis and disease progression, both in vitro and in vivo , thus providing the pre-clinical evidences for extremely attractive targets for novel therapeutic interventions in WM. Of note, recent evidences have also approached and defined the transcriptome profiling of WM cells, revealing a signature that mirrors the somatic aberrations demonstrated within the tumor clone. A parallel research field has also reported on microRNAs (miRNAs), highlighting the oncogenic role of miRNA-155 in WM. In the present review, we focus on the latest reports on genomics and miRNAs in WM, providing an overview of the clinical relevance of the latest acquired knowledge about genomics and miRNA aberrations in WM.
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- 2017
41. Biological and clinical implications of BIRC3 mutations in chronic lymphocytic leukemia
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Francesca Romana Mauro, Sruthi Sagiraju, Davide Rossi, Giovanni Del Poeta, Denise Peroni, Silvia Rasi, Ken I. Mills, Gian Matteo Rigolin, Sarah Lawless, Riccardo Bomben, Ilaria Del Giudice, Annalisa Chiarenza, Robin Foà, Francesca Arruga, Fary Diop, Alessio Bruscaggin, Marina Motta, Luca Laurenti, Marta Coscia, Ramesh Adhinaveni, Lorenzo De Paoli, Patrick Thornton, Phil Weir, Chiara Favini, Simone Favini, Riccardo Moia, Roberto Marasca, Carlo Visco, Antonio Cuneo, Omar Perbellini, Antonia Follenzi, Lodovico Terzi-di-Bergamo, Francesca Rossi, Renzo Boldorini, Andrea Patriarca, Alessandra Tedeschi, Clara Deambrogi, Ahad Ahmed Kodipad, Elisa Spaccarotella, Mark Catherwood, Chiara Tarantelli, Clive Jabangwe, Valeria Spina, Francesco Forconi, Francesco Bertoni, Francesco Zaja, David Donaldson, Valter Gattei, Gianluca Gaidano, Agostino Cortelezzi, Silvia Deaglio, Diop, F., Moia, R., Favini, C., Spaccarotella, E., De Paoli, L., Bruscaggin, A., Spina, V., Terzi-Di-Bergamo, L., Arruga, F., Tarantelli, C., Deambrogi, C., Rasi, S., Adhinaveni, R., Patriarca, A., Favini, S., Sagiraju, S., Jabangwe, C., Kodipad, A. A., Peroni, D., Mauro, F. R., Del Giudice, I., Forconi, F., Cortelezzi, A., Zaja, F., Bomben, R., Rossi, F. M., Visco, C., Chiarenza, A., Rigolin, G. M., Marasca, R., Coscia, M., Perbellini, O., Tedeschi, A., Laurenti, L., Motta, M., Donaldson, D., Weir, P., Mills, K., Thornton, P., Lawless, S., Bertoni, F., Poeta, G. D., Cuneo, A., Follenzi, A., Gattei, V., Boldorini, R. L., Catherwood, M., Deaglio, S., Foa, R., Gaidano, G., and Rossi, D.
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Oncology ,medicine.medical_specialty ,Cyclophosphamide ,Chronic lymphocytic leukemia ,chronic lymphocytic leukemia ,BIRC-3 ,prognosis ,medicine.disease_cause ,Chronic Lymphocytic Leukemia ,Cytogenetics and Molecular Genetics ,Molecular predictors ,Article ,NO ,03 medical and health sciences ,0302 clinical medicine ,Chemoimmunotherapy ,Internal medicine ,medicine ,Univariate analysis ,Mutation ,BIRC3 CLL prognosis ,business.industry ,Hematology ,medicine.disease ,Settore MED/15 ,3. Good health ,Fludarabine ,Leukemia ,Settore MED/15 - MALATTIE DEL SANGUE ,Birc3 ,IGHV@ ,business ,030215 immunology ,medicine.drug - Abstract
BIRC3 is a recurrently mutated gene in chronic lymphocytic leukemia (CLL) but the functional implications of BIRC3 mutations are largely unexplored. Furthermore, little is known about the prognostic impact of BIRC3 mutations in CLL cohorts homogeneously treated with first-line fludarabine, cyclophosphamide, and rituximab (FCR). By immunoblotting analysis, we showed that the non-canonical nuclear factor-κB pathway is active in BIRC3-mutated cell lines and in primary CLL samples, as documented by the stabilization of MAP3K14 and by the nuclear localization of p52. In addition, BIRC3-mutated primary CLL cells are less sensitive to flu-darabine. In order to confirm in patients that BIRC3 mutations confer resistance to fludarabine-based chemoimmunotherapy, a retrospective multicenter cohort of 287 untreated patients receiving first-line FCR was analyzed by targeted next-generation sequencing of 24 recurrently mutated genes in CLL. By univariate analysis adjusted for multiple comparisons BIRC3 mutations identify a poor prognostic subgroup of patients in whom FCR treatment fails (median progression-free survival: 2.2 years, P
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- 2019
42. MONITORAMENTO DE MÉDIOS E GRANDES MAMÍFEROS NA ESTAÇÃO ECOLÓGICA ÁGUAS EMENDADAS
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Marina Motta de Carvalho, Carlos Alberto da Cruz Júnior, Ana Mikaely Peixôto, Natália Cavalcante de Farias, and Rodrigo Augusto Lima Santos
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Microbiology (medical) ,Immunology ,Immunology and Allergy - Abstract
O Cerrado é o segundo maior bioma da América do Sul apresentando 5% da biodiversidade mundial e também é o segundo bioma brasileiro que mais sofreu ações antrópicas. Embora o Cerrado tenha a sua importância biológica reconhecida apenas 8,21% do seu território é protegido a partir de unidades de conservação (UC’s). As UC’s do Cerrado são de extrema importância para a preservação da biodiversidade desse bioma, em especial para a proteção da mastofauna de médio e grande porte, visto que os mamíferos são bastantes afetados pela degradação e fragmentação dos habitats naturais. Foi realizado o monitoramento de médios e grandes mamíferos na Estação Ecológica Águas Emendadas (ESEC-AE) e a partir dos registros obtidos foi elaborado o relatório qualitativo. O monitoramento foi realizado da segunda quinzena de Setembro de 2017 à segunda quinzena de Janeiro de 2018 com o auxílio de armadilhas fotográficas. Nesse período foram identificadas nove espécies de mamíferos distribuídas em quatro ordens: Artiodactyla, Carnivora, Perissodactyla e Rodentia. As espécies registradas foram: Cerdocyon thous, Chrysocyon brachyurus, Cuniculus paca, Dasyprocta azarae, Mazama spp, Nasua nasua, Puma concolor, Puma yagouaroundi e Tapirus terrestris. Das espécies de mamíferos detectadas, 44,44% são frugívoras e quatro encontram-se na Lista Nacional Oficial de Espécies da Fauna Ameaçadas de Extinção segundo a Portaria MMA 444/2014 – Chrysocyon brachyurus, Puma concolor, Puma yagouroundi e Tapirus terrestris. Os resultados obtidos reforçam a importância das UC’s para a conservação da fauna do Cerrado, uma vez que nesses sítios são encontrados exemplares ameaçados da mastofauna desse bioma, bem como demonstrou a eficiência do uso de armadilhas fotográficas para o monitoramento de mamíferos
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- 2018
43. MONITORAMENTO DE PEQUENOS MAMÍFEROS NÃO VOADORES EM UMA ÁREA DE CERRADO NO CÓRREGO DO URUBU, BRASÍLIA-DF
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Letícia Mendes Batista, Rodrigo Augusto Lima Santos, Marina Motta de Carvalho, Flávia Luanne Monteiro Barrêto, and Carlos Alberto da Cruz Júnior
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Microbiology (medical) ,Immunology ,Immunology and Allergy - Abstract
O Núcleo Rural Córrego do Urubu está situado a 14 quilômetros da rodoviária do Plano Piloto, na unidade hidrográfica Santa Maria/Torto (bacia hidrográfica do lago Paranoá), inserida em duas importantes Áreas de Proteção Ambiental (APA), a do Planalto Central e a do Lago Paranoá. Essa região vem sofrendo forte pressão antrópica em especial pela especulação imobiliária. A concretização desse feito certamente influenciará na dinâmica populacional de pequenos mamíferos da área e assim a pesquisa se mostrou urgente e poderá fornecer informações relevantes de comparação pós distúrbio sobre a população de pequenos mamíferos do local. Com o objetivo de entender os padrões de dispersão, fluxo de populações e estimar a riqueza e biodiversidade na área, realizou-se o monitoramento de pequenos mamíferos não voadores na Estação Experimental de agroecologia Chácara Delfim T61, localizada no Núcleo Rural Córrego do Urubu. As campanhas foram realizadas de janeiro/2018 a agosto/2018, no início de cada mês, por cinco dias consecutivos, em duas fitofisionomias: cerrado típico e campo sujo. Na área de cerrado típico, que apresentou maior riqueza e abundância, foi disposta uma grade formada por 7 transectos lineares, com 12 pontos cada, distantes 10m um do outro, totalizando 84 pontos de captura. Na área de fitofisionomia campo sujo foi disposta uma grade formada por 6 transectos lineares, com 11 pontos cada, distantes 10m um do outro, o que equivale ao total de 66 pontos de captura. Para captura e contenção dos animais foram utilizadas armadilhas do tipo Sherman e Tomahawk (124 e 26, respectivamente), com iscas compostas por fubá, sardinha, banana e pasta de amendoim. Para todos os espécimes capturados, foram realizadas medições biométricas, através de fita métrica e pesola, e estes foram identificados quanto ao sexo e estágio de desenvolvimento. Por fim, os animais foram marcados com brincos numerados para identificação em caso de recaptura. Foi registrado um total de 47 indivíduos capturados com 36 recapturas estes dentre três espécies de roedores (Necromys lasiurus, Oligoryzomys e Cerradomys scotti) e duas de marsupiais (Didelphis albiventris e Gracilinanus agilis). Necromys lasiurus e Didelphis albiventris foram as espécies maior estimativa, com 69,41% e 20% do total de indivíduos, respectivamente, e juntas equivalem a 82,9% dos indivíduos capturados e 97,36% dos recapturados. Os resultados obtidos poderão ser utilizados para estudo e definição de projetos que certamente influenciarão na dinâmica populacional de pequenos mamíferos da área
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- 2018
44. Overcoming the Supportive Stroma-Induced Proliferation in Waldenstrom's Macroglobulinemia By Selective Inhibition of the FGF/FGF-Receptor Axis
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Gaia C. Ghedini, Marco Presta, Antonino Neri, Antonio Sacco, Aldo M. Roccaro, Katia Todoerti, Silvia Giliani, Vanessa Favasuli, Marina Motta, Arianna Giacomini, Gaetana Lanzi, Giuseppe Rossi, Riccardo Castelli, Cinzia Federico, Marco Mor, Roberto Ronca, Nicole Bozza, and Antonella Anastasia
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Multicatalytic endopeptidase complex ,MTOR Serine-Threonine Kinases ,education ,Immunology ,Disease progression ,Tumor cells ,Cell Biology ,Hematology ,Selective inhibition ,Biochemistry ,Management ,Animal model ,Inhibitory concentration 50 ,FGF Receptor ,Business ,health care economics and organizations - Abstract
The human fibroblast growth factor receptor (FGF-R) family plays an essential role in a wide range of cellular processes, such as cell growth, proliferation, differentiation, migration and survival. It has been reported that FGF-Rs are expressed in hematopoietic cells; and FGF/FGFR signaling deregulation is largely involved in hematologic malignancies, including Waldenström macroglobulinemia (WM). WM is still an incurable disease, and patients succumb due to disease progression. Therefore, novel therapeutics designed to specifically target deregulated signaling pathways in WM are required. We aimed to investigate the role of FGF/FGF-R system in FGF-dependent WM cell lines by using an anti-pan FGF trap molecule (NSC12), responsible for FGF/FGF-R blocking. We first interrogated the GSE9656 dataset in order to confirm the expression of FGFs and FGF-Rs in WM cells, demonstrating an enrichment of several FGF- and FGF-R-isoforms in primary WM patients' derived tumor cells compared to the normal cellular counterpart (P Disclosures Ronca: Associazione Italiana per la Ricerca sul Canctro (AIRC): Research Funding. Rossi:Astellas: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Mundipharma: Honoraria; BMS: Honoraria; Sandoz: Honoraria; Amgen: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo: Consultancy; Roche: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Roccaro:AstraZeneca: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Associazione Italiana per al Ricerca sul Cancro (AIRC): Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; European Hematology Association: Research Funding; Associazione Italiana per al Ricerca sul Cancro (AIRC): Research Funding; Transcan2-ERANET: Research Funding; AstraZeneca: Research Funding; European Hematology Association: Research Funding; Transcan2-ERANET: Research Funding.
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- 2019
45. Waldenström's Macroglobulinemia (WM) Is Preceded By Clonal Lymphopoiesis Including MYD88 L265P in Progenitor B Cells
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Ibai Goicoechea, Diego Alignani, Cristina Pérez Ruiz, Amaia Vilas-Zornoza, Cirino Botta, Juan José Garcés, Ramón García-Sanz, Bruno Paiva, Sonia Garate, Jose A. Martinez-Climent, María José Calasanz, Marta Larrayoz, María José Larrayoz, Sara Rodriguez, Marina Motta, Christian Reinhardt, Isidro Sánchez-García, Rafael Valdés-Mas, Yolanda R. Carrasco, Susana Constantino Rosa Santos, Aitziber López, Sarvide Sarai, Antonio Sacco, Aldo M. Roccaro, Massimo Gentile, María José García-Barchino, Catarina Geraldes, Sara Duarte, Jesús F. San-Miguel, Helena Vitória, Giuseppe Rossi, Cristina Jimenez, Felipe Prosper, Artur Paiva, and Jon Celay
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Oncology ,medicine.medical_specialty ,business.industry ,Immunology ,CD34 ,Macroglobulinemia ,Germinal center ,Waldenstrom macroglobulinemia ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,medicine.anatomical_structure ,Internal medicine ,Cancer cell ,medicine ,Hairy cell leukemia ,Lymphopoiesis ,business ,B cell - Abstract
Background: The transformation from a normal to a cancer cell is driven by the multistep acquisition of genetic alterations. Recently, shared mutations between clonal B cells in MBL/CLL and CD34+ hematopoietic progenitor cells (HPC) have been identified. Similarly, a HPC origin of BRAFV600E mutations in hairy cell leukemia (HCL) has been uncovered, strengthening the notion that at least a fraction of somatic mutations may occur in CD34+ HPC before the malignant transformation of some B cell neoplasms. Since almost all WM patients have mutated MYD88L265P, it is worthy to investigate if this disease follows a similar pathogenic process than that of MBL/CLL or HCL. Aim: Define the cellular origin of WM by comparing the genetic landscape of WM cells to that of CD34+ HPC, B cell precursors and residual normal B cells. Methods: We used FACSorting to isolate 57 cell subsets from bone marrow (BM) aspirates of 10 WM patients: CD34+ HPC, B cell precursors, residual normal B cells (if detectable), WM B cells, plasma cells (PCs) and T cells (germline control). Whole-exome sequencing (WES, mean depth 79x) was performed with 10XGenomics Exome Solution for low DNA-input due to limited numbers of some cell types. Single-cell RNA and B-cell receptor sequencing (scRNA/BCRseq) was performed in total BM B cells and PCs (n=32,720) from 3 IgM MGUS and 2 WM patients. Accordingly, the clonotypic BCR detected in WM cells was unbiasedly investigated in all B cell maturation stages defined according to their molecular phenotype. In parallel, MYD88p.L252P (orthologous position of the human L265P mutation) transgenic mice were crossed with conditional Sca1Cre, Mb1Cre, and Cγ1Cre mice to selectively induce in vivo expression of MYD88 mutation in CD34+ HPC, B cell precursors and germinal center B cells, respectively. Upon immunization, mice from each cohort were necropsied at 5, 10 and 15 months. Results: All 10 WM patients showed MYD88L265P and 3 had mutated CXCR4. Notably, we found MYD88L265P in B cell precursors from 1/10 cases and in residual normal B cells from 4/10 patients, which were confirmed by ASO-PCR and ddPCR. Indeed, these more sensitive methods detected MYD88L265P in B cell precursors from 6/10 cases and in residual normal B cells from 6/10 patients. CXCR4 was simultaneously mutated in B cell precursors and WM B cells from one patient. Overall, CD34+ HPC, B-cell precursors and residual normal B cells shared a median of 2 (range, 0-45; mean VAF, 0.13), 3 (range, 1-44; mean VAF, 0.168), and 6 (range, 1-56; mean VAF, 0.29) somatic mutations with WM B cells; some being found all the way from CD34+ HPC to WM B cells and PCs. Interestingly, concordance between the mutational landscape of WM B cells and PCs was A median of 18 mutations (range, 3-26; median CCF and range, 0.72 [0.07 - 1]) were unique to WM cells. Importantly, clonal mutations in WM B cells were undetectable in normal cells. Thus, the few WM subclonal mutations observed in patients' lymphopoiesis could not result from contamination during FACSorting since in such cases, WM clonal mutations would become detectable in normal cells. Furthermore, copy number alterations (CNA) present in WM cells were undetectable in normal cells. scRNA/BCRseq unveiled that clonotypic cells were confined mostly within mature B cell and PC clusters in IgM MGUS, whereas a fraction of clonotypic cells from WM patients showed a transcriptional profile overlapping with that of B cell precursors. scRNA/BCRseq also uncovered transcriptional differences between clonal B cells from IgM MGUS vs WM patients (eg, proliferation, metabolism). In mice, induced expression of mutated MYD88 led to a moderate increase in the number of B220+CD138+ plasmablasts and B220-CD138+ PCs in lymphoid tissues and BM, but no signs of clonality or hematological disease. Interestingly, such increment was more evident in mice with activation of mutated MYD88 in CD34+ HPC and B-cell precursors vs mice with MYD88 L252P induced in germinal center B cells. Conclusions: We show for the first time that WM patients have somatic mutations, including MYD88L265P and CXCR4 at the B cell progenitor level. Taken together, this study suggests that in some patients, WM could develop from B cell clones carrying MYD88L265P rather than being the initiating event, and that other mutations or CNA are required for the expansion of B cells and PCs with the WM phenotype. Disclosures Motta: Roche: Honoraria; Janssen: Honoraria. Rossi:Astellas: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Advisory board; Abbvie: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Jazz: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Garcia-Sanz:Takeda: Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Gilead: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Amgen: Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Self: Patents & Royalties: BIOMED-2 PRIMERS FOR CLONALITY ASSESSMENT; IVS technologies: Consultancy, Patents & Royalties; Novartis: Research Funding. Roccaro:Transcan2-ERANET: Research Funding; European Hematology Association: Research Funding; Amgen: Other; AstraZeneca: Research Funding; Celgene: Other; Janssen: Other; Italian Association for Cancer Research (AIRC): Research Funding. San-Miguel:Amgen, BMS, Celgene, Janssen, MSD, Novartis, Takeda, Sanofi, Roche, Abbvie, GlaxoSmithKline and Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees. Paiva:Sanofi: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; SkylineDx: Consultancy; Takeda: Consultancy, Honoraria, Research Funding; Roche: Research Funding; Adaptive: Honoraria; Amgen: Honoraria; Janssen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Kite: Consultancy.
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- 2019
46. Waldenström Macroglobulinemia in Young Patients Treated in the Modern Era: A Multi-Institutional Italian Study
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Sara Rattotti, Marina Motta, Francesco Piazza, Vittorio Del Fabro, Angela Ferrari, Michele Merli, Giulia Benevolo, Carlo Visco, Luca Laurenti, Alessandra Tedeschi, Virginia Valeria Ferretti, Rita Rizzi, Antonio Abbadessa, Corinna Greco, Stefano Luminari, Marzia Varettoni, Andrea Corbingi, Marina Deodato, Catherine Klersy, and Luca Arcaini
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Oncology ,medicine.medical_specialty ,Urinary bladder ,business.industry ,medicine.medical_treatment ,Immunology ,Cancer ,Waldenstrom macroglobulinemia ,Cell Biology ,Hematology ,Immunotherapy ,medicine.disease ,Biochemistry ,Chemotherapy regimen ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,Internal medicine ,Ibrutinib ,medicine ,Rituximab ,business ,Neoadjuvant therapy ,medicine.drug - Abstract
Background. Waldenström Macroglobulinemia (WM) is a rare indolent lymphoma typical of the elderly population, with a median age at diagnosis of 65-70 years and median overall survival of approximately 10 years. Age is the most important prognostic factor in WM, and unrelated mortality significantly impacts survival in elderly patients. The past two decades have witnessed important treatment advances in WM, with the introduction of anti-CD20 monoclonal antibodies in the early 2000s and of ibrutinib in more recent years. Less than 10% of WM patients are diagnosed at young age, and few studies have addressed their characteristics and outcome in the era of immunotherapy and targeted therapies. Here we report the presenting features, treatment and outcome of WM patients younger than 55 years diagnosed in 12 Hematologic Centers across Italy between 2000 and 2018. Patients and Methods. Diagnostic criteria were those established during the second International Workshop on WM (Owen et al, 2003) and were retrospectively applied to patients diagnosed before 2003. The overall survival (OS) observed in the study cohort was compared with the expected survival of the general Italian population matched by sex, age and calendar year. The expected survival estimates were derived from Italian life tables (Istituto Nazionale di Statistica, ISTAT). Results. The median age of patients included in the study was 50 years (interquartile range, IQR: 46-52). Their clinical characteristics at diagnosis are reported in Table 1. With a median follow-up of 5.6 years (IQR 3.1-9.1), 76 of 129 patients (59%) have been treated, at diagnosis (n=31, 41%) or after initial observation (n=45, 59%). The median treatment-free survival was 39 months. According to ISS-WM prognostic score, 58% were classified as low risk, 30% as intermediate risk and 12% as high risk. Frontline therapy included Rituximab in 71/76 patients (93%). Rituximab was associated with chemotherapy in 62 patients (82%), whereas 9 patients (12%) received a chemo-free induction. Five patients (7%) received chemotherapy only as first-line therapy (Table 2). The overall response rate (ORR) to induction therapy was 85%, including 39% CR+VGPR. Two patients received Rituximab maintenance for 2 years. The median progression-free survival (PFS) after first-line therapy was 76 months. Four of 76 patients (5%) received an autologous stem cell transplantation at relapse/progression. Overall, 14/76 patients (18%) received ibrutinib as first (n=2) or as subsequent line of therapy (n=12). During follow-up, 4/76 patients (5%) developed a solid cancer (bladder n=2, breast n=1, prostate n=1) and 2 a second hematologic cancer (chronic myelomonocytic leukemia n=1, secondary MDS n=1). Using a competing-risk model, accounting for death from any cause as the competing event, the cumulative incidence of second cancers was 2% at 5 years and 5.8% at 10 years. Three patients have died, 2 due to WM and 1 due to acute myeloid leukemia. The 5-and 10-year OS from diagnosis were 99% and 96% respectively. In a time-dependent survival analysis, considering therapy as a time-dependent covariate, the OS of treated and untreated WM patients was not significantly different (P = 0.162) (Figure 1). Among treated patients, the OS was significantly shorter in high-risk patients as compared with low- and intermediate-risk patients (5-year OS 85.7% versus 100%, P=0.018) (Figure 2). The OS of young WM patients was not significantly reduced as compared with age-, sex- and calendar year- matched general population (P > 0.05) (Figure 3). Conclusions. The presenting features of young WM patients resemble those typically described in the elderly WM population. Among treated patients, more than half are low-risk according to ISS-WM, confirming age as the most important prognostic factor. More than 90% of patients received Rituximab as part of the upfront treatment, mainly in combination with chemotherapy. Ibrutinib seems to be preferred over autologous stem cell transplantation in the relapsed/refractory setting. The outcome of young WM patients treated in Italy in the contemporary era was excellent in terms of both PFS and OS, with a life expectancy not significantly reduced as compared with the general population. Figure 1 Disclosures Varettoni: Gilead: Other: travel expenses; Janssen: Consultancy; Roche: Consultancy; ABBVIE: Other: travel expenses. Tedeschi:AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Janssen spa: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BeiGene: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SUNESIS: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy. Benevolo:Novartis Pharmaceuticals: Consultancy. Del Fabro:Janssen: Consultancy. Luminari:ROCHE: Other: Role as Advisor ; CELGENE: Other: Role as Advisor & Travel Grant; TAKEDA: Other: Travel Grant; GILEAD: Other: Lecturer . Arcaini:Gilead Sciences: Research Funding; Celgene: Speakers Bureau; Celgene, Roche, Janssen-Cilag, Gilead: Other: Travel expenses; Bayer, Celgene, Gilead Sciences, Roche, Sandoz, Janssen-Cilag, VERASTEM: Consultancy.
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- 2019
47. Primary Analysis of Anti-CD19 Tafasitamab (MOR208) Treatment in Combination with Idelalisib or Venetoclax in R/R CLL Patients Who Failed Prior BTK Inhibitor Therapy (COSMOS Trial)
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Philipp B. Staber, Richard Greil, Marina Motta, Maren Dirnberger-Hertweck, Stephan Stilgenbauer, Asher Chanan-Khan, Andrzej Hellmann, Clemens-Martin Wendtner, Wojciech Jurczak, Johannes Weirather, Jennifer A. Woyach, Dietger Niederweiser, Wolfram Brugger, Jan Moritz Middeke, Marco Montillo, Peter Kelemen, Peter Neumeister, Talha Munir, Vladan Vucinic, Sameer A. Parikh, and Johannes Schetelig
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Oncology ,medicine.medical_specialty ,biology ,Venetoclax ,business.industry ,Chronic lymphocytic leukemia ,Immunology ,Cell Biology ,Hematology ,Neutropenia ,medicine.disease ,Biochemistry ,chemistry.chemical_compound ,chemistry ,Ibrutinib ,Internal medicine ,medicine ,biology.protein ,Bruton's tyrosine kinase ,Acalabrutinib ,Idelalisib ,business ,Adverse effect - Abstract
Introduction: Patients (pts) with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) who failed treatment with the Bruton's tyrosine kinase inhibitor (BTKi) ibrutinib have a poor outcome and are difficult to treat. This ongoing, two-cohort, Phase II trial evaluates the safety and preliminary efficacy of tafasitamab (MOR208), an Fc-enhanced anti-CD19 monoclonal antibody in combination with idelalisib (IDE) (Cohort A) or venetoclax (VEN) (Cohort B) in R/R CLL pts previously treated with a BTKi. Preliminary results were published at EHA 2018 for Cohort A and at ASH 2018 for Cohort B. Here, we report the results of the primary analysis for both cohorts. Methods and Patients: Pts who either progressed or were intolerant to BTKi were enrolled at 12 sites in six countries in Europe and the US from Nov 2016 to Apr 2018. The primary endpoint is the incidence and severity of adverse events (AEs); secondary endpoints include overall response rate (ORR) as per investigator assessment according to International Workshop on CLL (IWCLL) 2008 guidelines. Complete response (CR) was confirmed by computed tomography assessment and by bone marrow (BM) biopsy. The exploratory endpoint minimal residual disease (MRD) was assessed centrally by quantitative allele-specific oligonucleotide-polymerase chain reaction (ASO-PCR) in peripheral blood (PB) and BM. Each treatment cycle (C) lasts 28 days (D). Dose and administration: tafasitamab intravenous infusion, 12 mg/kg weekly in C1-C3, every other week in C4-C6 and monthly from C7D1; IDE orally, 150 mg twice daily; VEN orally, weekly ramp up starting on C1D8 at 20 mg to full daily dose of 400 mg. Patients: mean time since first CLL diagnosis was 135 months (mos) for pts in Cohort A and 105 mos in Cohort B. Median number of prior therapy lines was five (2-9) and three (1-5), respectively. All pts had received ibrutinib; one pt had subsequent acalabrutinib treatment as last prior therapy line. Mutations of BTK and PLCγ2 were assessed in nine pts in Cohort A and 13 pts in Cohort B. BTK/PLCγ2 mutations were centrally detected in 4/3 pts in Cohort A and in 2/3 pts in Cohort B, respectively. Complex karyotype was observed in six (54.5%) pts in Cohort A and 12 (92.3%) pts in Cohort B. Results with a data cut-off date of 9 Nov 2018 are presented. Results: Cohort A: Median time on study was 9.9 mos (95% confidence interval [CI]: 5.7-not reached). Eleven pts were enrolled and received tafasitamab and IDE. Two pts discontinued treatment due to AEs (aspartate-aminotransferase increased; acute pancreatitis), two due to progressive disease (PD) and one pt by physician's decision. One pt died due to PD and one pt due to cardiac failure. At the cut-off date, treatment was ongoing in four pts. Table 1 summarizes treatment-emergent adverse events (TEAEs) with neutropenia Grade ≥3 being most common (5 [46%]). Fourteen treatment-emergent serious AEs (SAEs) were reported in eight (72.7%) pts. ORR was 90.9% (CR=9.1%, partial response [PR]=81.8%), disease control was achieved in all 11 pts. One of eight pts (12.5%) assessed for MRD status reached MRD-negativity in PB at C14. Cohort B: Median time on study was 12 mos (95% CI: 2.8-not reached). Eleven of 13 enrolled pts received tafasitamab and VEN while two pts received tafasitamab only. Three pts discontinued treatment due to AEs (infusion-related reactions [two pts], diarrhea [one pt], one due to PD and one withdrew consent. At the cut-off date, treatment was ongoing in eight patients. Table 2 summarizes TEAEs, neutropenia Grade ≥3 was most commonly observed (six [46%] pts). Fourteen SAEs were reported in nine (69.2%) pts. The ORR in all 13 pts was 76.9% (CR=23.1%, PR=53.8%, not evaluable=23.1%). Six of seven pts assessed for MRD in PB (46.2% of 13 [100%] pts) reached negative status in PB by C7 at the latest. One of three pts assessed for MRD in BM (7.7% of 13 [100%] pts) reached MRD negative status in BM at C15. Conclusions: This trial demonstrates that in heavily pretreated pts with R/R CLL who failed prior BTKi, tafasitamab in combination with IDE or VEN is a potential therapeutic option. The safety profiles of the combinations are influenced by the combination partner, but both combinations are manageable. The response rates and MRD-negativity rates indicate that combinations of targeted agents with anti-CD19 tafasitamab have valuable antitumor activity and warrant further investigation of tafasitamab-based combinations in CLL. Disclosures Staber: AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Honoraria, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda-Millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Jurczak:Celtrion: Research Funding; Sandoz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Morphosys: Research Funding; Celgene Corporation: Research Funding; Incyte: Research Funding; Servier: Research Funding; Roche: Research Funding; Novo Nordisk: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Research Funding; Gilead: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Loxo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; TG Therapeutics: Research Funding. Brugger:AstraZeneca: Equity Ownership; MorphoSys: Employment. Chanan-Khan:Pharmacyclics: Research Funding; Merck: Research Funding; Jansen: Research Funding; Mayo Clinic: Employment; Ascentage: Research Funding; Millennium: Research Funding; Xencor: Research Funding; AbbVie: Research Funding. Greil:Mundipharma: Honoraria, Research Funding; Bristol-Myers-Squibb: Consultancy, Honoraria, Other: Travel/accomodation expenses, Research Funding; Daiichi Sankyo: Consultancy, Honoraria; Sanofi Aventis: Honoraria; Sandoz: Honoraria; AstraZeneca: Consultancy, Honoraria, Other: Travel/accomodation expenses, Research Funding; Celgene: Consultancy, Honoraria, Other: Travel/accomodation expenses, Research Funding; Eisai: Honoraria; Janssen-Cilag: Honoraria; Cephalon: Consultancy, Honoraria, Research Funding; Genentech: Honoraria, Research Funding; Merck: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Other: Travel/accomodation expenses, Research Funding; Boehringer Ingelheim: Honoraria; Amgen: Consultancy, Honoraria, Other: Travel/accomodation expenses, Research Funding; Ratiopharm: Research Funding; Takeda: Consultancy, Honoraria, Research Funding; MSD: Consultancy, Honoraria, Other: Travel/accomodation expenses, Research Funding; Pfizer: Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Other: Travel/accomodation expenses, Research Funding; Roche: Consultancy, Honoraria, Other: Travel/accomodation expenses, Research Funding; GSK: Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Dirnberger-Hertweck:MorphoSys: Employment. Kelemen:MorphoSys: Employment. Middeke:Janssen: Consultancy, Speakers Bureau; MSD: Consultancy; AbbVie: Consultancy, Speakers Bureau; Gilead: Consultancy; Roche: Speakers Bureau; Sanofi: Research Funding, Speakers Bureau. Montillo:Roche: Consultancy, Honoraria, Research Funding; Acerta: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; AstraZeneca: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Speakers Bureau; Versatem: Membership on an entity's Board of Directors or advisory committees. Munir:Acerta: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Other: TBC; AbbVie: Honoraria; Alexion: Honoraria; Gilead: Honoraria; Janssen: Honoraria; Novartis: Honoraria; Roche: Honoraria; Morphosys: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sunesis: Consultancy. Parikh:Pharmacyclics: Honoraria, Research Funding; Ascentage Pharma: Research Funding; Genentech: Honoraria; MorphoSys: Research Funding; Acerta Pharma: Research Funding; AbbVie: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; Janssen: Research Funding. Stilgenbauer:Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Hoffmann La-Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Weirather:MorphoSys: Employment. Woyach:Janssen: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; AbbVie: Research Funding; Karyopharm: Research Funding; Loxo: Research Funding; Morphosys: Research Funding; Verastem: Research Funding. Wendtner:AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau; Hoffman-La Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead Sciences, Inc.: Consultancy, Honoraria, Research Funding, Speakers Bureau; MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.
- Published
- 2019
48. Outcome of Patients with Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL) Treated with Ibrutinib within a Named Patient Program (NPP) in Italy. a Real-Life Retrospective Study
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Annamaria Frustaci, Agostino Cortelezzi, Stefano Molica, Marina Motta, Paolo de Fabritiis, Luca Laurenti, Paola Fazi, Lorella Orsucci, Pier Luigi Zinzani, Lydia Scarfò, Carmelo Carlo-Stella, Francesca Romana Mauro, Robin Foà, Lucia Farina, Marco Vignetti, Gianluca Gaidano, Monica Tani, Stefano Soddu, Franca Falzetti, Antonio Cuneo, Marco Gobbi, Roberto Marasca, Nicola Di Renzo, Marta Coscia, and Francesco Zaja
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Prior treatment ,medicine.medical_specialty ,business.industry ,Immunology ,Disease progression ,Retrospective cohort study ,Cell Biology ,Hematology ,Biochemistry ,Sudden death ,Discontinuation ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,chemistry ,030220 oncology & carcinogenesis ,Ibrutinib ,Family medicine ,Relapsed refractory ,Ischemic stroke ,Medicine ,business ,030215 immunology - Abstract
Introduction. Observational, real-life studies are relevant to understand whether data derived from prospective controlled trials (CTs) are reproducible in the day-to-day clinical practice. Within a named patient program (NPP), free and early access to ibrutinib was made available for the treatment of relapsed/refractory (R/R) patients with chronic lymphocytic leukemia (CLL) until this agent was approved in Italy. To define the efficacy and toxicity profile of patients treated with ibrutinib in this real-life setting, the GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) group carried out a retrospective analysis on the outcome of R/R patients with CLL who received ibrutinib in the NPP. Methods. Between April 2014 and January 2015, 216 R/R patients with CLL managed at 20 centers in Italy were included in the NPP. Patients were required to have R/R disease with disease progression within 24 months after prior chemo-immunotherapy. All patients received ibrutinib at the standard dose of 420 mg daily, continuously until disease progression or unacceptable toxicity. The period of observation included the duration of the NPP and was extended up to January 2016 for patients still on treatment with the commercial drug. Clinical data were reported retrospectively by the treating physicians using the Research Electronic Data Capture (REDCap) system. Results. The median age of patients was 58.3 years (range 27.5-81); 89% of patients were in Binet stage B-C. The median number of prior treatments was 3 (range 1-14). Thirty-seven % of patients was refractory to prior treatment. Deletion 17p and/or TP53 mutations were found in 54% of patients and deletion 11q in 11.6%. Seventy-eight % of patients had an unmutated IGHV gene profile. Prior atrial fibrillation (AF) was reported in 13 cases (6%), while 7 patients with AF (3.3%) were on anti-arrythmic treatment. Hypertension was recorded in 76 cases (35.2%). The median follow-up of patients was 24 months (range, 1-24 months. A response to ibrutinib was observed in 172 patients (79.6%) with a clinical CR/CRi in 34 (15.7%) and a PR/PR-L in 138 (63.9%). Similar response rates were observed in patients with an unmutated IGHV gene status (82.1%) and in those with deletion 17p/TP53 mutations (79.6%). The progression-free survival (PFS) and overall survival (OS) at 24 months were 64.6% (95%CI: 58.0-71.9) and 72.7% (95%CI: 66.5-79.4), respectively. No differences in PFS and OS were observed according to the IGHV mutational status (IGHV unmutated vs mutated: PFS, 65.2% vs 61.0%; p=0.7; OS, 65.2% vs 72.0%, p=0.6) and the presence of TP53 aberrations (TP53 aberrations, present vs absent: PFS, 64.8% vs 64.1%; p=0.6; OS, 69.8% vs 72.7%; p=0.8). Forty-eight patients (22.2%) discontinued ibrutinib within 12 months and 22 (10.2%) within 12-24 months from the start of ibrutinib. Progressive disease and Richter syndrome were the most common reasons for discontinuation that accounted for 16.2% (35 patients) and 1.8% (4 patients) of cases, respectively, and occurred after a median of 17 months from the start of ibrutinib. Treatment discontinuations due to adverse events (AEs) were recorded in 25 patients (11.6%) after a median time of 6 months from the start of treatment and included infections/febrile events in 7 cases, bleeding events in 3 (intracranial hemorrhage 1), sudden death in 3, acute myocardial infarction in 1, ischemic stroke in 2, second malignancy in 3, diarrhea in 1. AF occurred during treatment in 14 (6.5%) patients and was the reason of ibrutinib discontinuation in 2. AEs leading to discontinuation was not specified in 3 cases. Other reasons for ibrutinib discontinuation in 6 (2.8%) patients were ASCT in 4, unplanned surgery in 1, unknown in 1. Survival probability at 12 months from treatment discontinuation due to AEs or DP/RS was 38.2 and 37.2 months respectively (p= 0.6). Conclusions. The results of this real-life study show that in unselected patients with R/R CLL the clinical activity of ibrutinib was comparable to that reported in CTs. However, a third of patients discontinued ibrutinib within 24 months from the start of treatment. An earlier introduction of ibrutinib in the treatment approach of R/R patients, a careful surveillance and management of toxicities will optimise the clinical benefits of ibrutinib in CLL patients treated in the clinical practice. Disclosures Mauro: Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Zinzani:TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astra Zeneca: Speakers Bureau; MSD: Honoraria, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SERVIER: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees. Cortelezzi:novartis: Consultancy; roche: Consultancy; abbvie: Consultancy; janssen: Consultancy. Carlo-Stella:AstraZeneca: Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Janssen: Speakers Bureau; Sanofi: Consultancy; ADC Therapeutics: Research Funding, Speakers Bureau; Boehringher Ingelheim Italia: Consultancy; Genenta Science: Speakers Bureau; Rhizen Pharmaceuticals: Research Funding; Amgen: Speakers Bureau; MSD Italia: Speakers Bureau. Molica:Roche: Other: Advisory board; Gilead: Other: Advisory board; Jansen: Other: Advisory board; AbbVie: Other: Advisory board. Coscia:Janssen, Karyopharm: Research Funding; Abbvie, Gilead, Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees. Zaja:Janssen: Honoraria; Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria; Takeda: Honoraria; Sandoz: Honoraria; Abbvie: Honoraria. Gaidano:Roche: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Morphosys: Honoraria; AbbVie: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Gobbi:Ariad: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; Amgen: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Pfister: Membership on an entity's Board of Directors or advisory committees. Cuneo:janssen: Other: advisory board, Speakers Bureau; Gilead: Other: advisory board, Speakers Bureau; Abbvie: Other: advisory board, Speakers Bureau; Roche: Other: advisory board, Speakers Bureau. Foà:JANSSEN: Other: ADVISORY BOARD, Speakers Bureau; NOVARTIS: Speakers Bureau; ROCHE: Other: ADVISORY BOARD, Speakers Bureau; ABBVIE: Other: ADVISORY BOARD, Speakers Bureau; AMGEN: Other: ADVISORY BOARD; CELTRION: Other: ADVISORY BOARD; GILEAD: Speakers Bureau; CELGENE: Other: ADVISORY BOARD, Speakers Bureau; INCYTE: Other: ADVISORY BOARD.
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- 2018
49. P077 Tuberculosis in inflammatory bowel disease patients from a referral center in Salvador-Bahia, Brazil
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Victor, Mariano, primary, Laíla, Andrade, additional, Fernanda, Oliveira, additional, Monique, Santos, additional, Fernanda, Pereira, additional, Claudia, dos Santos, additional, Neogélia, Almeida, additional, Valdiana, Surlo, additional, Marina, Motta, additional, Maria, Fortes Flora, additional, Andréa, Pimentel, additional, Jaciane, Fontes, additional, and Genoile, Santana, additional
- Published
- 2019
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50. Factors predicting survival in chronic lymphocytic leukemia patients developing Richter syndrome transformation into Hodgkin lymphoma
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Roberta Murru, Alessandra Tedeschi, Alessandro Gozzetti, Anna Guarini, Robin Foà, Fortunato Morabito, Giovanni Del Poeta, Anna Maria Frustaci, Melissa Campanelli, Sara Raponi, Luca Laurenti, Piero Galieni, Gianluigi Reda, Idanna Innocenti, Maria D Caputo, Francesca Romana Mauro, Marina Motta, and Massimo Gentile
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Oncology ,Male ,Chronic lymphocytic leukemia ,0302 clinical medicine ,immune system diseases ,Risk Factors ,hemic and lymphatic diseases ,Neoplasms ,Antineoplastic Combined Chemotherapy Protocols ,80 and over ,Adult ,Aged ,Aged, 80 and over ,Bleomycin ,Combined Modality Therapy ,Dacarbazine ,Doxorubicin ,Female ,Hodgkin Disease ,Humans ,Immunoglobulin Heavy Chains ,Leukemia, Lymphocytic, Chronic, B-Cell ,Middle Aged ,Mutation ,Neoplasms, Second Primary ,Prognosis ,Remission Induction ,Retrospective Studies ,Treatment Outcome ,Vinblastine ,Hematology ,Chronic ,Leukemia ,Lymphocytic ,Fludarabine ,Second Primary ,B symptoms ,030220 oncology & carcinogenesis ,medicine.symptom ,medicine.drug ,medicine.medical_specialty ,ABVD Regimen ,03 medical and health sciences ,Internal medicine ,medicine ,business.industry ,B-Cell ,medicine.disease ,Settore MED/15 ,Settore MED/15 - MALATTIE DEL SANGUE ,ABVD ,Immunology ,business ,030215 immunology - Abstract
We hereby report the clinical and biologic features of 33 of 4680 (0.7%) patients with chronic lymphocytic leukemia (CLL), managed at 10 Italian centers, who developed Hodgkin lymphoma (HL), a rare variant of Richter syndrome. The median age at CLL and at HL diagnosis were 61 years (range 41-80) and 70 years (range 46-82), respectively, with a median interval from CLL to the diagnosis of HL of 90 months (range 0-258). In 3 cases, CLL and HL were diagnosed simultaneously. Hl was characterized by advanced stage in 79% of cases, International Prognostic Score (IPS) ≥4 in 50%, extranodal involvement in 39%, B symptoms in 70%. Prior treatment for CLL had been received by 82% of patients and included fludarabine in 67%. Coexistence of CLL and HL was detected in the same bioptic tissue in 87% of cases. The most common administered treatment was the ABVD regimen given to 22 patients (66.6%). The complete response (CR) rate after ABVD was 68%, and was influenced by the IPS (P = .03) and interval from the last CLL treatment (P = .057). Survival from HL was also influenced by the IPS (P = .006) and time from the last CLL treatment (P = .047). The achievement of CR with ABVD was the only significant and independent factor predicting survival (P = .037). Taken together, our results show that the IPS and the interval from the prior CLL treatment influence the likelihood of achieving CR after ABVD, which is the most important factor predicting survival of patients with CLL developing HL.
- Published
- 2017
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