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1. Long-term analysis of the RiBVD phase II trial reveals the unfavorable impact of TP53 mutations and hypoalbuminemia in older adults with mantle cell lymphoma; for the LYSA group

Author: Sylvain Carras, Alexia Torroja, Anouk Emadali, Emilie Montaut, Nicolas Daguindau, Adrian Tempescul, Anne Moreau, Emmanuelle Tchernonog, Anna Schmitt, Roch Houot, Caroline Dartigeas, Sarah Barbieux, Selim Corm, Anne Banos, Ludovic Fouillet, Jehan Dupuis, Margaret Macro, Joel Fleury, Fabrice Jardin, Clementine Sarkozy, Ghandi Damaj, Pierre Feugier, Luc Matthieu Fornecker, Cecile Chabrot, Veronique Dorvaux, Krimo Bouabdallah, Sandy Amorim, Reda Garidi, Laurent Voillat, Bertrand Joly, Nadine Morineau, Marie Pierre Moles, Hacene Zerazhi, Jean Fontan, Yazid Arkam, Magda Alexis, Vincent Delwail, Jean Pierre Vilque, Loic Ysebaert, Barbara Burroni, Mary Callanan, Steven Le Gouill, and Rémy Gressin
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Between 2011 and 2012, a phase II trial evaluated the use of the RiBVD (rituximab, bendamustine, velcade and dexamethasone) combination as first-line treatment for mantle cell lymphoma (MCL) patients over the age of 65. We have now re-examined the classic prognostic factors, adding an assessment of TP53 mutation status. Patients (N=74; median age 73 years) were treated with the RiBVD combination. Median progression-free survival (mPFS) was 79 months and median overall survival (mOS) was 111 months. TP53 mutation status was available for 54/74 (73%) patients. TP53 mutations (TP53mt) were found in 12 patients (22.2%). In multivariate analysis, among the prognostic factors (PF) evaluated, only TP53mt and an albumin level (Alb) 3.6 g/dL were independently associated with a shorter mPFS. A hazard ratio (HR) of 3.16 (1.3-9.9, P=0.014) was obtained for TP53mt versus TP53 wild-type (wt), and 3.6 (1.39-9.5, P=0.009) for Alb
Published: 2023
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2. P315: TP53 ALTERATIONS AND MRD REFINE PROGNOSIS OF ADULT KMT2A-REARRANGED B-ALL

Author: Rathana Kim, Hugo Bergugnat, Florence Pasquier, Emmanuel Raffoux, Lise Larcher, Marie Passet, Cedric Pastoret, Grardel Nathalie, Vahid Asnafi, Eric Delabesse, Aurélie Caye-Eude, Claus Meyer, Rolf Masrschalek, Anne Thiebaut-Bertrand, Marie Balsat, Martine Escoffre, Sabine Blum, Michael Baumann, Anne Banos, Nicole Straetmans, Maria Pilar Gallego Hernanz, Yves Chalandon, Carlos Graux, Thibaut Leguay, Mathilde Hunault, Françoise Huguet, Véronique Lhéritier, Jean Soulier, Nicolas Boissel, and Emmanuelle Clappier
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Published: 2023
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3. A phase II study of guadecitabine in higher-risk myelodysplastic syndrome and low blast count acute myeloid leukemia after azacitidine failure

Author: Marie Sébert, Aline Renneville, Cécile Bally, Pierre Peterlin, Odile Beyne-Rauzy, Laurence Legros, Marie-Pierre Gourin, Laurence Sanhes, Eric Wattel, Emmanuel Gyan, Sophie Park, Aspasia Stamatoullas, Anne Banos, Kamel Laribi, Simone Jueliger, Luke Bevan, Fatiha Chermat, Rosa Sapena, Olivier Nibourel, Cendrine Chaffaut, Sylvie Chevret, Claude Preudhomme, Lionel Adès, and Pierre Fenaux
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: High-risk myelodysplastic syndrome/acute myeloid leukemia patients have a very poor survival after azacitidine failure. Guadecitabine (SGI-110) is a novel subcutaneous hypomethylating agent which results in extended decitabine exposure. This multicenter phase II study evaluated the efficacy and safety of guadecitabine in high-risk myelodysplastic syndrome and low blast count acute myeloid leukemia patients refractory or relapsing after azacitidine. We included 56 patients with a median age of 75 years [Interquartile Range (IQR) 69-76]. Fifty-five patients received at least one cycle of guadecitabine (60 mg/m2/d subcutaneously days 1-5 per 28-day treatment cycles), with a median of 3 cycles (range, 0-27). Eight (14.3%) patients responded, including two complete responses; median response duration was 11.5 months. Having no or few identified somatic mutations was the only factor predicting response (P=0.035). None of the 11 patients with TP53 mutation responded. Median overall survival was 7.1 months, and 17.9 months in responders (3 of whom had overall survival >2 years). In multivariate analysis, IPSS-R (revised International Prognostic Scoring System) score other than very high (P=0.03) primary versus secondary azacitidine failure (P=0.01) and a high rate of demethylation in blood during the first cycle of treatment (P=0.03) were associated with longer survival. Thus, guadecitabine can be effective, sometimes yielding relatively prolonged survival, in a small proportion of high-risk myelodysplastic syndrome/low blast count acute myeloid leukemia patients who failed azacitidine. (Trial registered at clinicaltrials.gov identifier: 02197676)
Published: 2019
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4. Aplastic anemia in the elderly: a nationwide survey on behalf of the French Reference Center for Aplastic Anemia

Author: Adrien Contejean, Matthieu Resche-Rigon, Jérôme Tamburini, Marion Alcantara, Fabrice Jardin, Etienne Lengliné, Lionel Adès, Didier Bouscary, Ambroise Marçais, Delphine Lebon, Cécile Chabrot, Louis Terriou, Fiorenza Barraco, Anne Banos, Lucile Bussot, Jean-Yves Cahn, Pierre Hirsch, Natacha Maillard, Laurence Simon, Luc-Matthieu Fornecker, Gerard Socié, Regis Peffault de Latour, and Flore Sicre de Fontbrune
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Aplastic anemia is a rare but potentially life-threatening disease that may affect older patients. Data regarding the treatment of aplastic anemia in this ageing population remains scarce. We conducted a retrospective nationwide multicenter study in France to examine current treatments for aplastic anemia patients over 60 years old. Our aims were to evaluate efficacy and tolerance, and to analyze predictive factors for response and survival. Over the course of a decade, 88 patients (median age 68.5 years) were identified in 19 centers, with a median follow up of 2.7 years; 21% had very severe and 36% severe aplastic anemia. We analyzed 184 treatment lines, mostly involving the standard combination of anti-thymocyte globulin and cyclosporine-A (33%), which was also the most frequent first-line treatment (50%). After first-line therapy, 32% of patients achieved a complete response, and 15% a partial response. Responses were significantly better in first line and in patients with good performance status, as well as in those that had followed an anti-thymocyte globulin and cyclosporine-A regimen (overall response rate of 70% after first-line treatment). All treatments were well tolerated by patients, including over the age of 70. Three-year survival was 74.7% (median 7.36 years). Age, Charlson comorbidity index and very severe aplastic anemia were independently associated with mortality. Age, per se, is not a limiting factor to aplastic anemia treatment with anti-thymocyte globulin and cyclosporine-A; this regimen should be used as a first-line treatment in elderly patients if they have a good performance status and low comorbidity index score.
Published: 2019
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5. A phase 2 study of rituximab, bendamustine, bortezomib and dexamethasone for first-line treatment of older patients with mantle cell lymphoma

Author: Rémy Gressin, Nicolas Daguindau, Adrian Tempescul, Anne Moreau, Sylvain Carras, Emmanuelle Tchernonog, Anna Schmitt, Roch Houot, Caroline Dartigeas, Jean Michel Pignon, Selim Corm, Anne Banos, Christiane Mounier, Jehan Dupuis, Margaret Macro, Joel Fleury, Fabrice Jardin, Clementine Sarkozy, Ghandi Damaj, Pierre Feugier, Luc Matthieu Fornecker, Cecile Chabrot, Veronique Dorvaux, Krimo Bouadallah, Sandy Amorin, Reda Garidi, Laurent Voillat, Bertrand Joly, Philippe Solal Celigny, Nadine Morineau, Marie Pierre Moles, Hacene Zerazhi, Jean Fontan, Yazid Arkam, Magda Alexis, Vincent Delwail, Jean Pierre Vilque, Loic Ysebaert, Steven Le Gouill, Mary B. Callanan, and for the Lymphoma Study Association
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: We present results of a prospective, multicenter, phase II study evaluating rituximab, bendamustine, bortezomib and dexamethasone as first-line treatment for patients with mantle cell lymphoma aged 65 years or older. A total of 74 patients were enrolled (median age, 73 years). Patients received a maximum of six cycles of treatment at 28-day intervals. The primary objective was to achieve an 18-month progression-free survival rate of 65% or higher. Secondary objectives were to evaluate toxicity and the prognostic impact of mantle cell lymphoma prognostic index, Ki67 expression, [18F]fluorodeoxyglucose-positron emission tomography and molecular minimal residual disease, in peripheral blood or bone marrow. With a median follow-up of 52 months, the 24-month progression-free survival rate was 70%, hence the primary objective was reached. After six cycles of treatment, 91% (54/59) of responding patients were analyzed for peripheral blood residual disease and 87% of these (47/54) were negative. Four-year overall survival rates of the patients who did not have or had detectable molecular residual disease in the blood at completion of treatment were 86.6% and 28.6%, respectively (P
Published: 2019
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6. Increased rituximab exposure does not improve response and outcome of patients with chronic lymphocytic leukemia after fludarabine, cyclophosphamide, rituximab. A French Innovative Leukemia Organization (FILO) study

Author: Guillaume Cartron, Rémi Letestu, Caroline Dartigeas, Mira Tout, Béatrice Mahé, Anne-Laure Gagez, Emmanuelle Ferrant, Boris Guiu, Bruno Villemagne, Phan Letuan, Thérèse Aurran, Frédérique Orsini-Piocelle, Anne Banos, Pierre Feugier, Véronique Leblond, Sophie de Guibert, Olivier Tournilhac, Jehan Dupuis, Alain Delmer, Valérie Rouillé, David Ternant, and Stéphane Leprêtre
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Published: 2018
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7. miR-125b and miR-532-3p predict the efficiency of rituximab-mediated lymphodepletion in chronic lymphocytic leukemia patients. A French Innovative Leukemia Organization study

Author: Anne-Laure Gagez, Isabelle Duroux-Richard, Stéphane Leprêtre, Frédérique Orsini-Piocelle, Rémi Letestu, Sophie De Guibert, Edouard Tuaillon, Véronique Leblond, Olfa Khalifa, Valérie Gouilleux-Gruart, Anne Banos, Olivier Tournilhac, Jehan Dupuis, Christian Jorgensen, Guillaume Cartron, and Florence Apparailly
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: The underlying in vivo mechanisms of rituximab action remain incompletely understood in chronic lymphocytic leukemia. Recent data suggest that circulating micro-ribonucleic acids correlate with chronic lymphocytic leukemia progression and response to rituximab. Our study aimed at identifying circulating micro-ribonucleic acids that predict response to rituximab monotherapy in chronic lymphocytic leukemia patients. Using a hierarchical clustering of micro-ribonucleic acid expression profiles discriminating 10 untreated patients with low or high lymphocyte counts, we found 26 micro-ribonucleic acids significantly deregulated. Using individual real-time reverse transcription polymerase chain reaction, the expression levels of micro-ribonucleic acids representative of these two clusters were further validated in a larger cohort (n=61). MiR-125b and miR-532-3p were inversely correlated with rituximab-induced lymphodepletion (P=0.020 and P=0.001, respectively) and with the CD20 expression on CD19+ cells (P=0.0007 and P
Published: 2017
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8. Analysis of renal impairment in MM-003, a phase III study of pomalidomide + low - dose dexamethasone versus high - dose dexamethasone in refractory or relapsed and refractory multiple myeloma

Author: Katja C. Weisel, Meletios A. Dimopoulos, Philippe Moreau, Martha Q. Lacy, Kevin W. Song, Michel Delforge, Lionel Karlin, Hartmut Goldschmidt, Anne Banos, Albert Oriol, Adrian Alegre, Christine Chen, Michele Cavo, Laurent Garderet, Valentina Ivanova, Joaquin Martinez-Lopez, Stefan Knop, Xin Yu, Kevin Hong, Lars Sternas, Christian Jacques, Mohamed H. Zaki, and Jesus San Miguel
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Pomalidomide + low-dose dexamethasone is effective and well tolerated for refractory or relapsed and refractory multiple myeloma after bortezomib and lenalidomide failure. The phase III trial MM-003 compared pomalidomide + low-dose dexamethasone with high-dose dexamethasone. This subanalysis grouped patients by baseline creatinine clearance ≥ 30 − < 60 mL/min (n=93, pomalidomide + low-dose dexamethasone; n=56, high-dose dexamethasone) or ≥ 60 mL/min (n=205, pomalidomide + low-dose dexamethasone; n=93, high-dose dexamethasone). Median progression-free survival was similar for both subgroups and favored pomalidomide + low-dose dexamethasone versus high-dose dexamethasone: 4.0 versus 1.9 months in the group with baseline creatinine clearance ≥ 30 − < 60 mL/min (P
Published: 2016
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9. Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma

Author: Jesus F. San Miguel, Katja C. Weisel, Kevin W. Song, Michel Delforge, Lionel Karlin, Hartmut Goldschmidt, Philippe Moreau, Anne Banos, Albert Oriol, Laurent Garderet, Michele Cavo, Valentina Ivanova, Adrian Alegre, Joaquin Martinez-Lopez, Christine Chen, Christoph Renner, Nizar Jacques Bahlis, Xin Yu, Terri Teasdale, Lars Sternas, Christian Jacques, Mohamed H. Zaki, and Meletios A. Dimopoulos
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Pomalidomide is a distinct oral IMiD® immunomodulatory agent with direct antimyeloma, stromal-support inhibitory, and immunomodulatory effects. The pivotal, multicenter, open-label, randomized phase 3 trial MM-003 compared pomalidomide + low-dose dexamethasone vs high-dose dexamethasone in 455 patients with refractory or relapsed and refractory multiple myeloma after failure of bortezomib and lenalidomide treatment. Initial results demonstrated significantly longer progression-free survival and overall survival with an acceptable tolerability profile for pomalidomide + low-dose dexamethasone vs high-dose dexamethasone. This secondary analysis describes patient outcomes by treatment history and depth of response. Pomalidomide + low-dose dexamethasone significantly prolonged progression-free survival and favored overall survival vs high-dose dexamethasone for all subgroups analyzed, regardless of prior treatments or refractory status. Both univariate and multivariate analyses showed that no variable relating to either the number (≤ or > 3) or type of prior treatment was a significant predictor of progression-free survival or overall survival. No cross-resistance with prior lenalidomide or thalidomide treatment was observed. Patients achieving a minimal response or better to pomalidomide + low-dose dexamethasone treatment experienced a survival benefit, which was even higher in those achieving at least a partial response (17.2 and 19.9 months, respectively, as compared with 7.5 months for patients with less than minimal response). These data suggest that pomalidomide + low-dose dexamethasone should be considered a standard of care in patients with refractory or relapsed and refractory multiple myeloma regardless of prior treatment. ClinicalTrials.gov: NCT01311687; EudraCT: 2010-019820-30.
Published: 2015
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10. Cytogenetics and long-term survival of patients with refractory or relapsed and refractory multiple myeloma treated with pomalidomide and low-dose dexamethasone

Author: Meletios A. Dimopoulos, Katja C. Weisel, Kevin W. Song, Michel Delforge, Lionel Karlin, Hartmut Goldschmidt, Philippe Moreau, Anne Banos, Albert Oriol, Laurent Garderet, Michele Cavo, Valentina Ivanova, Adrian Alegre, Joaquin Martinez-Lopez, Christine Chen, Andrew Spencer, Stefan Knop, Nizar J. Bahlis, Christoph Renner, Xin Yu, Kevin Hong, Lars Sternas, Christian Jacques, Mohamed H. Zaki, and Jesus F. San Miguel
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Patients with refractory or relapsed and refractory multiple myeloma who no longer receive benefit from novel agents have limited treatment options and short expected survival. del(17p) and t(4;14) are correlated with shortened survival. The phase 3 MM-003 trial demonstrated significant progression-free and overall survival benefits from treatment with pomalidomide plus low-dose dexamethasone compared to high-dose dexamethasone among patients in whom bortezomib and lenalidomide treatment had failed. At an updated median follow-up of 15.4 months, the progression-free survival was 4.0 versus 1.9 months (HR, 0.50; P
Published: 2015
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11. Phase II study of bendamustine, bortezomib and dexamethasone as second-line treatment for elderly patients with multiple myeloma: the Intergroupe Francophone du Myelome 2009-01 trial

Author: Philippe Rodon, Cyrille Hulin, Brigitte Pegourie, Mourad Tiab, Bruno Anglaret, Lotfi Benboubker, Henry Jardel, Olivier Decaux, Brigitte Kolb, Murielle Roussel, Laurent Garderet, Xavier Leleu, Olivier Fitoussi, Carine Chaleteix, Philippe Casassus, Pascal Lenain, Bruno Royer, Anne Banos, Riad Benramdane, Pascale Cony-Makhoul, Mamoun Dib, Jean Fontan, Anne-Marie Stoppa, Catherine Traullé, Jean-Pierre Vilque, Marie-Odile Pétillon, Claire Mathiot, Thomas Dejoie, Hervé Avet-Loiseau, and Philippe Moreau
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Published: 2015
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12. Treatment with lenalidomide does not appear to increase the risk of progression in lower risk myelodysplastic syndromes with 5q deletion. A comparative analysis by the Groupe Francophone des Myelodysplasies

Author: Lionel Adès, Fabien Le Bras, Marie Sebert, Charikleia Kelaidi, Thierry Lamy, François Dreyfus, Virginie Eclache, Jacques Delaunay, Didier Bouscary, Sorin Visanica, Pascal Turlure, Agnès Guerci Bresler, Marie-Paule Cabrol, Anne Banos, Michel Blanc, Norbert Vey, Alain Delmer, Eric Wattel, Sylvie Chevret, and Pierre Fenaux
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Background Although lenalidomide is very effective in the treatment of anemia of lower risk myelodysplastic syndromes with 5q deletion (del 5q), concerns have been raised over the fact that this drug could trigger progression to acute myeloid leukemia in some patients.Design and Methods Ninety-five transfusion-dependent patients with lower risk myelodysplastic syndromes with del 5q were treated with lenalidomide (10 mg/day, for 3 weeks every 4 weeks); six (6.3%) of the patients progressed to acute myeloid leukemia. This cohort of 95 lenalidomide-treated patients was compared to a historical control cohort of 99 patients with lower risk myelodysplastic syndromes with del 5q who never received lenalidomide, using a propensity score approach that can control for potential confounders in non-randomized comparisons.Results The 4-year estimated cumulative incidence of leukemia was 9% in patients treated with lenalidomide and 15.8% in controls who did not receive lenalidomide (P=0.16).Conclusions Using a propensity score approach, we found no significant difference in acute myeloid leukemia progression and survival from diagnosis between the cohort treated with lenalidomide and the control cohort.
Published: 2012
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13. Targeting RARA overexpression with tamibarotene, a potent and selective RARα agonist, is a novel approach in AML

Author: Stéphane de Botton, Thomas Cluzeau, Carlos Vigil, Rachel J. Cook, Philippe Rousselot, David A. Rizzieri, Jane L. Liesveld, Pierre Fenaux, Thorsten Braun, Anne Banos, Joseph G. Jurcic, Mikkael A. Sekeres, Michael R. Savona, Gail J. Roboz, Dale Bixby, Kate Madigan, Angela Volkert, Kristin Stephens, Qing Kang-Fortner, Kristen Baker, Sofia Paul, Michael McKeown, John Carulli, Matthew Eaton, Graeme Hodgson, Christopher Fiore, Michael J. Kelly, David A. Roth, and Eytan M. Stein
Subjects: Hematology
Abstract: A superenhancer at the retinoic acid receptor alpha (RARA) gene is associated with RARA mRNA overexpression in ∼30% of non-acute promyelocytic leukemia acute myeloid leukemia (AML) and in ∼50% of myelodysplastic syndromes (MDS). RARA overexpression is an actionable target for treatment with tamibarotene, an oral potent and selective RARα agonist. Sensitivity to the RARα agonist tamibarotene was demonstrated in RARA-high but not RARA-low preclinical AML models. The combination of oral tamibarotene plus azacitidine was evaluated in a phase 2 clinical study in 51 newly diagnosed unfit patients with AML identified as RARA-positive (n = 22) or RARA-negative (n = 29) for RARA mRNA overexpression in peripheral blasts using a blood-based biomarker test. In 18 response-evaluable RARA-positive patients, complete remission (CR)/CR with incomplete hematologic recovery rate was 61%, CR rate was 50%, and time to initial composite CR was rapid at 1.2 months. Transfusion independence was attained by 72% of RARA-positive patients. In contrast, 28 response-evaluable RARA-negative patients had response rates that were consistent with azacitidine monotherapy. Tamibarotene in combination with azacitidine was well tolerated. The majority of nonhematologic adverse events were low grade and hematologic adverse events were comparable to single-agent azacitidine, demonstrating that there was no additional myelosuppression when tamibarotene was combined with azacitidine. These results support further evaluation of tamibarotene-based treatment strategies in patients with AML or MDS with RARA overexpression to provide a targeted approach with the goal of improving patient outcomes. This trial was registered at www.clinicaltrials.gov as #NCT02807558.
Published: 2023

14. Addition of Brentuximab Vedotin to Gemcitabine in Relapsed or Refractory T-Cell Lymphoma: Final Analysis of a Lysa Multicenter, Phase II Study. 'the TOTAL Trial'

Author: Olivier Tournilhac, Solene Lecolant, Maya Hacini, Krimo Bouabdallah, Sebastien Bailly, Kamel Laribi, Thibaut Belmondo, Marie Maerevoet, Loic Ysebaert, Stéphanie Guidez, Steven Le Gouill, Christophe Bonnet, Marc Andre, Jehan Dupuis, Catherine Thieblemont, Emmanuel Bachy, Nicolas Daguindau, Franck Morschhauser, Sabine Tricot, Pierre Feugier, Anne Banos, Thierry Lamy, Adrien Chauchet, Emmanuel Gyan, Guillaume Cartron, Hassan Farhat, Vincent Camus, Bernard Drenou, Hacene Zerazhi, David Sibon, Emmanuelle Nicolas-Virelizier, Caroline Delette, Sylvia Snauwaert, Nicole Straetmans, Richard Delarue, Marie Parrens, Samuel Griolet, Philippe Gaulard, Marie-Helene Delfau-Larue, Laurence De Leval, and Gandhi Laurent Damaj
Subjects: Immunology, Cell Biology, Hematology, Biochemistry
Published: 2022

15. A Phase II prospective trial of azacitidine in steroid-dependent or refractory systemic autoimmune/inflammatory disorders and VEXAS syndrome associated with MDS and CMML

Author: Arsene Mekinian, Lin Pierre Zhao, Sylvie Chevret, Kristell Desseaux, Laurent Pascal, Thibaut Comont, Alexandre Maria, Pierre Peterlin, Louis Terriou, Maud D’Aveni Piney, Marie-Pierre Gourin, Norbert Vey, Odile Beyne Rauzy, Vincent Grobost, Holy Bezanahary, Sophie Dimicoli-Salazar, Anne Banos, Stefan Wickenhauser, Benoit De Renzis, Eric Durot, Shanti Natarajan-Amé, Laurent Voillat, Fatiha Chermat, Karine Lemaire, Vincent Jachiet, Chantal Himberlin, Sylvain Thépot, Jose Miguel Torregrosa Diaz, Laurent Frenzel, Emmanuel Gyan, Guillaume Denis, Pierre Hirsch, Olivier Kosmider, Lionel Ades, Olivier Fain, and Pierre Fenaux
Subjects: Cancer Research, Oncology, Hematology
Published: 2022

16. A fixed-duration, immunochemotherapy approach in CLL: 5.5-year results from the phase 2 ICLL-07 FILO trial

Author: Anne-Sophie Michallet, Rémi Letestu, Magali Le Garff-Tavernier, Lydia Campos, Michel Ticchioni, Marie-Sarah Dilhuydy, Stephane MORISSET, Valerie Rouille, Beatrice Mahe, Kamel Laribi, Bruno Villemagne, Emmanuelle France Ferrant, Olivier Tournilhac, Alain Jacques Delmer, Lysiane Molina, Veronique Leblond, Cécile TOMOWIAK, Sophie De Guibert, Frederique Orsini Piocelle, Anne Banos, Philippe Carassou, Guillaume Cartron, Luc-Matthieu Fornecker, Loïc Ysebaert, Caroline Dartigeas, Malgorzata Truchan-Graczyk, Jean-Pierre Vilque, Thérèse Aurran Schleinitz, Florence Cymbalista, Stéphane Leprêtre, Vincent Lévy, Florence Nguyen-Khac, and Pierre Feugier
Subjects: Hematology
Abstract: In previously untreated, medically fit patients with chronic lymphocytic leukemia, research is focused on developing fixed-duration strategies to improve long-term outcomes whilst sparing patients from serious toxicities. The ICLL-07 trial evaluated a fixed-duration (15-month) immunochemotherapy approach where, following obinutuzumab-ibrutinib induction for 9 months, patients (n=10) in complete remission (CR) with bone marrow (BM) measurable residual disease (MRD)
Published: 2023

17. Dexaml-02 : A Phase II Study of Dexamethasone Added to Induction and Postremission Therapy in Older Patients with Newly Diagnosed AML. a French Innovative Leukemia Organization (FILO) Study

Author: Christian Recher, Sarah Bertoli, Pierre Peterlin, Romain Guieze, Yohan Desbrosses, Yosr Hicheri, Omar Benbrahim, Martin Carre, Hunault-Berger Mathilde, Anne Banos, Marc Bernard, Emmanuel Gyan, Alain Saad, Safia Chebrek, Gabrielle Roth Guepin, Veronique Dorvaux, Laurence Sanhes, Maria Pilar Gallego Hernanz, Carole Exbrayat, Laure Vincent, Chantal Himberlin, Laetitia Largeaud, Eric Delabesse, Francois Vergez, Norbert Vey, Ariane C Mineur, Célestine Simand, Isabelle Luquet, and Arnaud Pigneux
Subjects: Immunology, Cell Biology, Hematology, Biochemistry
Published: 2022

18. A Fixed-Duration Immunochemotherapy Approach Combined with Ibrutinib in CLL Produces Deep and Sustained MRD Responses: 5.5-Year Results from the Icll-07 Filo Trial

Author: Anne-Sophie Michallet, Rémi Letestu, Magali Le Garff-Tavernier, Carmen Aanaei, Michel Ticchioni, Marie-Sarah Dilhuydy, Stephane Morisset, Valérie Rouille, Béatrice Mahé, Kamel Laribi, Bruno Villemagne, Emmanuelle Ferrant, Olivier Tournilhac, Alain Delmer, Christelle Portois, Lysiane Molina, Véronique Leblond, Cécile Tomowiak, Sophie de Guibert, Frederique Orsini, Anne Banos, Philippe Carassou, Guillaume Cartron, Luc Mathieu Fornecker, Loic Ysebaert, Caroline Dartigeas, Margot Truchan, Jean-Pierre Vilque, Therese Aurran Schleinitz, Cymbalista Florence, Stéphane Leprêtre, Vincent Lévy, Florence Nguyen Khac, and Pierre Feugier
Subjects: Immunology, Cell Biology, Hematology, Biochemistry
Published: 2022

19. Epag 2015 : A Phase II Randomized Placebo-Controlled Study to Assess the Impact on Outcome of Eltrombopag Administered to Elderly Patients with Acute Myeloid Leukemia Receiving Induction Chemotherapy. a French Innovative Leukemia Organization (FILO) Study

Author: Arnaud Pigneux, Pierre-Yves Dumas, Marc Bernard, Norbert Vey, Audrey Bidet, Ariane Mineur, Mathilde Hunault, Martin Carre, Mario Ojeda, Anne Banos, Pierre Peterlin, Romain Guieze, Yohan Desbrosses, Gabrielle Roth Guepin, Celestine Simand, Thibaut Leguay, Emmanuel Gyan, Eric Jourdan, Jean-Philippe Vial, Tony Marchand, Yosr Hicheri, Marie C Bene, Jean Francois Hamel, and Christian Recher
Subjects: Immunology, Cell Biology, Hematology, Biochemistry
Published: 2022

20. Haemolytic paroxysmal nocturnal haemoglobinuria in patients with myeloid neoplasms: A rare association with specific therapeutic implications

Author: Aurélien Sutra del Galy, Lise Willems, Maud D'Aveni, Cécile Pautas, Sylvain Chantepie, Benjamin Carpentier, Fiorenza Barraco, Anne Banos, Reda Garidi, Edouard Forcade, Flore Sicre de Fontbrune, and Régis Peffault de Latour
Subjects: Hematology
Published: 2023

21. Salvage therapy with brentuximab-vedotin and bendamustine for patients with R/R PTCL: a retrospective study from the LYSA

Author: Raphaelle Aubrais, Krimo Bouabdallah, loic chartier, Charles Herbaux, Anne Banos, Pauline Brice, David Sibon, Jean Marc Schiano, Thomas Cluzeau, Kamel Laribi, Ronan LE CALLOCH, Mathieu bellal, Baptiste Delapierre, nicolas daguindau, Sandy Amorim, Kossi Agbetiafa, Adrien Chauchet, caroline besson, Eric Durot, Christophe Bonnet, Ludovic Fouillet, Fontanet Bijou, Olivier Tournilhac, Philippe Gaulard, Marie-Cécile Parrens, and Gandhi Damaj
Subjects: Hematology
Abstract: Purpose: Patients with Relapsed or Refractory (R/R) Peripheral T cell Lymphomas (PTCL) have a poor prognosis. Bendamustine (B) and Brentuximab Vedotin (Bv) have shown interesting results in this setting. However, little information is available about their efficacy in combination. Patients and Methods: This multicenter and retrospective study aimed to evaluate the efficacy and safety of the combination of BBv in patients with non-cutaneous R/R PTCL among 21 LYSA centers in France and Belgium. The primary objective was the overall response rate. Results: Eighty-two patients with R/R PTCL were included. The best ORR was 68%, with 49% of patients in CR. In multivariable analysis, only the relapse status after the last regimen (relapse vs refractory) was associated with the response with an ORR of 83% vs 57% (OR=3.70 (95%CI:1.3-10.5); p=0.014). Median DoR was 15.4 (0.6-50.2) months for patients in CR. With a median follow-up of 22 (0-52) months, the median PFS and OS were 8.3 and 26.3 months respectively. Moreover, patients in CR, who underwent an allogeneic transplant, had a better outcome than patients who did not with a median PFS and OS of 19.3 versus 4.8 months (p=0.0005) and NR versus 12.4 months (p=0.0013) respectively. Fifty-nine percent of patients experienced grade 3/4 adverse events which were mainly hematologic. Conclusion: BBv is highly active in patients with R/R PTCL and should be considered as a one of the best option of immunochemotherapy salvage combination in this setting and particularly as a bridge to allogeneic transplant for eligible patients.
Published: 2022

22. Gilteritinib activity in refractory or relapsed FLT3-mutated acute myeloid leukemia patients previously treated by intensive chemotherapy and midostaurin: a study from the French AML Intergroup ALFA/FILO

Author: Pierre-Yves Dumas, Emmanuel Raffoux, Emilie Bérard, Sarah Bertoli, Marie-Anne Hospital, Maël Heiblig, Yohann Desbrosses, Caroline Bonmati, Cécile Pautas, Juliette Lambert, Corentin Orvain, Anne Banos, Florence Pasquier, Pierre Peterlin, Tony Marchand, Madalina Uzunov, Jamilé Frayfer, Pascal Turlure, Thomas Cluzeau, Eric Jourdan, Chantal Himberlin, Emmanuelle Tavernier, Alban Villate, Stephanie Haiat, Marie-Lorraine Chretien, Martin Carre, Sylvain Chantepie, Ioana Vaida, Mathieu Wemeau, Safia Chebrek, Gaelle Guillerm, Romain Guièze, Houria Debarri, Eve Gehlkopf, Kamel Laribi, Ambroise Marcais, Alberto Santagostino, Marie-Christine Béné, Ariane Mineur, Arnaud Pigneux, Hervé Dombret, and Christian Récher
Subjects: Cancer Research, Oncology, Hematology
Abstract: The real-world efficacy and safety of gilteritinib was assessed in an ambispective study that included 167 R/R FLT3-mutated AML patients. Among them, 140 received gilteritinib as single agent (cohort B), including 67 previously treated by intensive chemotherapy and midostaurin (cohort C). The main differences in patient characteristics in this study compared to the ADMIRAL trial were ECOG ≥ 2 (83.6% vs. 16.6%), FLT3-TKD mutation (21.0% vs. 8.5%), primary induction failure (15.0% vs. 40.0%) and line of treatment (beyond 2nd in 37.1% vs. 0.0%). The rates of composite complete remission, excluding those that occurred after hematopoietic stem cell transplantation (HSCT), were similar at respectively 25.4% and 27.5% in cohorts B and C. Median overall survival (OS) for these two groups was also similar at respectively 6.4 and 7.8 months. Multivariate analyses for prognostic factors associated with OS identified female gender (HR 1.61), adverse cytogenetic risk (HR 2.52), and allogenic HSCT after gilteritinib (HR 0.13). Although these patients were more heavily pretreated, these real-world data reproduce the results of ADMIRAL and provide new insights into the course of patients previously treated by intensive chemotherapy and midostaurin and beyond the 2nd line of treatment who can benefit from treatment in an outpatient setting.
Published: 2022

23. Reduced peripheral blood dendritic cell and monocyte subsets in MDS patients with systemic inflammatory or dysimmune diseases

Author: Vincent, Jachiet, Laure, Ricard, Pierre, Hirsch, Florent, Malard, Laurent, Pascal, Odile, Beyne-Rauzy, Pierre, Peterlin, Alexandre Thibault Jacques, Maria, Norbert, Vey, Maud, D'Aveni, Marie-Pierre, Gourin, Sophie, Dimicoli-Salazar, Anne, Banos, Stefan, Wickenhauser, Louis, Terriou, Benoit, De Renzis, Eric, Durot, Shanti, Natarajan-Ame, Anne, Vekhoff, Laurent, Voillat, Sophie, Park, Julien, Vinit, Céline, Dieval, Azeddine, Dellal, Vincent, Grobost, Lise, Willems, Julien, Rossignol, Eric, Solary, Olivier, Kosmider, Nicolas, Dulphy, Lin Pierre, Zhao, Lionel, Adès, Pierre, Fenaux, Olivier, Fain, Mohamad, Mohty, Béatrice, Gaugler, and Arsène, Mekinian
Abstract: Systemic inflammatory and autoimmune diseases (SIADs) occur in 10-20% of patients with myelodysplastic syndrome (MDS). Recently identified VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome, associated with somatic mutations in UBA1 (Ubiquitin-like modifier-activating enzyme 1), encompasses a range of severe inflammatory conditions along with hematological abnormalities, including MDS. The pathophysiological mechanisms underlying the association between MDS and SIADs remain largely unknown, especially the roles of different myeloid immune cell subsets. The aim of this study was to quantitatively evaluate peripheral blood myeloid immune cells (dendritic cells (DC) and monocytes) by flow cytometry in MDS patients with associated SIAD (n = 14, most often including relapsing polychondritis or neutrophilic dermatoses) and to compare their distribution in MDS patients without SIAD (n = 23) and healthy controls (n = 7). Most MDS and MDS/SIAD patients had low-risk MDS. Eight of 14 (57%) MDS/SIAD patients carried UBA1 somatic mutations, defining VEXAS syndrome.Compared with MDS patients, most DC and monocyte subsets were significantly decreased in MDS/SIAD patients, especially in MDS patients with VEXAS syndrome. Our study provides the first overview of the peripheral blood immune myeloid cell distribution in MDS patients with associated SIADs and raises several hypotheses: possible redistribution to inflammation sites, increased apoptosis, or impaired development in the bone marrow.
Published: 2022

24. Conventional chemotherapy for acute myeloid leukemia in older adults: Impact on nutritional, cognitive, and functional status

Author: Christian Recher, Eric Jourdan, Anne Banos, Claire Jouzier, Franciane Paul, Bruno Lioure, Romain Guieze, Norbert Ifrah, Pierre-Yves Dumas, Caroline Bonmati, Arnaud Pigneux, Jean-François Hamel, Mathilde Hunault, Jean-Yves Cahn, Jean-Christophe Ianotto, Mario Ojeda-Uribe, Marc Bernard, Norbert Vey, Marie-Christine Béné, Hacene Zerazhi, Jacques Delaunay, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Bordeaux [Bordeaux], Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Clermont-Ferrand, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Strasbourg, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Henri Duffaut (Avignon), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Aix Marseille Université (AMU), Assistance Publique - Hôpitaux de Marseille (APHM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Activities of daily living, MESH: Cognition, 0302 clinical medicine, Cognition, MESH: Aged, 80 and over, Nutritional status, Activities of Daily Living, Prospective Studies, MESH: Geriatric Assessment, Aged, 80 and over, MESH: Aged, Cognitive status, MESH: Middle Aged, Myeloid leukemia, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, General Medicine, MESH: Follow-Up Studies, Middle Aged, MESH: Nutritional Status, Leukemia, Myeloid, Acute, 030220 oncology & carcinogenesis, Older adults, Cohort, Toxicity, Functional status, Female, MESH: Leukemia, Myeloid, Acute, medicine.medical_specialty, Context (language use), Antineoplastic Agents, 03 medical and health sciences, Internal medicine, medicine, Humans, neoplasms, Aged, Acute myeloid leukemia, MESH: Humans, business.industry, MESH: Activities of Daily Living, Geriatric assessment, MESH: Male, MESH: Prospective Studies, MESH: Antineoplastic Agents, business, MESH: Female, 030215 immunology, Follow-Up Studies
Abstract: International audience; Objectives: The impact of conventional treatment for acute myeloid leukemia (AML) on the nutritional, cognitive, and functional status of elderly patients is seldom studied. This assessment was performed in the context of the LAMSA 2007 trial.Methods: The trial enrolled 424 patients with de novo AML. Among them, 316 benefited from geriatric assessment (GA) including nutritional, cognitive, and functional status and were scored according to Eastern Cooperative Oncology Group (ECOG) and sorror for the prediction of treatment toxicity, morbidity, and mortality. Patients were investigated at diagnosis for three times during follow-up.Results: This study showed that AML and its treatment have no impact on cognitive (P = .554) nor functional status (P = .842 for Activity of Daily Living and P = .087 for Instrumental Activities of Daily Living). The nutritional status improved over time (P = .041). None of these three parameters at baseline, associated or not with ECOG and sorror scores, impacted survivals or toxicities.Conclusions: The cognitive, functional, and nutritional status had no impact in this cohort of fit elderly AML patients without unfavorable cytogenetics. The GA tools used provided no additional information compared with ECOG and sorror scores, to predict toxicity, morbidity, or mortality due to intensive chemotherapy.
Published: 2021

25. Oncology nurse phone calls halve the risk of reduced dose intensity of immunochemotherapy: results of the randomized FORTIS study in chronic lymphocytic leukemia

Author: Carla Araujo, Marie Larcher, Gisèle Compaci, Lucie Oberic, Agnès Sommet, Anne Banos, Guy Laurent, Laurence Sahnes, Loic Ysebaert, and Fabien Despas
Subjects: Male, Oncology, medicine.medical_specialty, Chronic lymphocytic leukemia, Psychological intervention, Disease-Free Survival, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Risk Factors, law, Internal medicine, Survivorship curve, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Progression-free survival, Cyclophosphamide, Aged, Hematology, business.industry, Oncology Nursing, General Medicine, Middle Aged, Reduced dose, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Survival Rate, Oncology nursing, 030220 oncology & carcinogenesis, Female, Immunotherapy, Rituximab, business, Vidarabine, 030215 immunology
Abstract: Delivering of 80% planned relative dose intensity (RDI) of fludarabine-cyclophosphamide-rituximab (FCR) is key to benefit from longer progression free survival (PFS) and survivals in CLL. In this randomized trial, we sought to investigate whether a telephone intervention strategy (called AMA) delivered by an oncology nurse could reduce the risk of RDI 80% by alleviating adverse events and supporting patients' adherence. Sixty FCR patients were randomized 1:1 for AMA (stratified on Binet stage C). As per guidelines, patients received pegfilgrastim as primary prophylaxis of febrile neutropenia. At the end of therapy, RDI 80% was reported in 31% of patients, shortening PFS (median 26 months versus not reached, P = 0.021) and OS at 3 years (100 vs 70%, P = 0.0089). Oncology nurse interventions tended to significantly reduce this event (RDI 80%: 41.4% in non-AMA versus 20.7% in AMA patients (p = 0.09)). By adjusting our logistic regression model on published parameters exposing to RDI 80%, we found that AMA protected significantly against the risk of reduced RDI (OR = 0.22, IC95% 0.05-0.84, p = 0.04), independently of grade 3/4 neutropenia ( 15% per cycle) and febrile neutropenia ( 5% per cycle) events. As a conclusion, we confirmed that 20% reduction of FCR dose-intensity was detrimental for PFS/OS, but that oncology nurse interventions reduced the risk of dose concessions.
Published: 2019

26. Aplastic anemia in the elderly: a nationwide survey on behalf of the French Reference Center for Aplastic Anemia

Author: Lucile Bussot, Anne Banos, Matthieu Resche-Rigon, Delphine Lebon, Fiorenza Barraco, Didier Bouscary, Jerome Tamburini, Natacha Maillard, Fabrice Jardin, Laurence Simon, Flore Sicre de Fontbrune, Ambroise Marçais, Adrien Contejean, Jean-Yves Cahn, Pierre Hirsch, Lionel Adès, Louis Terriou, Régis Peffault de Latour, Gérard Socié, Marion Alcantara, Etienne Lengliné, Luc Mathieu Fornecker, Cécile Moluçon-Chabrot, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut national du cancer [Boulogne] (INCA)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), CIC - Biotherapie - GHU Ouest APHP (CIC-BT 502), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Université de Paris (UP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], University Paris Descartes Sorbonne Paris Cité, Imagine Institute, Paris, CHU Amiens-Picardie, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Claude Huriez [Lille], CHU Lille, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital de Bayonne, CH de la Côte Basque, Centre Hospitalier Universitaire [Grenoble] (CHU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Strasbourg, service hématologie Strasbourg, Service d’Hématologie Biologique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), DESSAIVRE, Louise, Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), CHU Necker - Enfants Malades [AP-HP], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Université Paris Diderot - Paris 7 (UPD7), Le CHCB, Centre Hospitalier de la Côte Basque, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and CHU Grenoble
Subjects: Pediatrics, medicine.medical_specialty, Population ageing, Palliative care, Anemia, [SDV]Life Sciences [q-bio], Immunology, Eltrombopag, Disease, 030204 cardiovascular system & hematology, Biochemistry, Article, chemistry.chemical_compound, 03 medical and health sciences, 0302 clinical medicine, Median follow-up, Surveys and Questionnaires, Severity of illness, medicine, Humans, Aplastic anemia, Aged, Antilymphocyte Serum, Performance status, business.industry, Bone marrow failure, Anemia, Aplastic, Standard of Care, Cell Biology, Hematology, medicine.disease, Bone Marrow Failure, 3. Good health, [SDV] Life Sciences [q-bio], Regimen, chemistry, 030220 oncology & carcinogenesis, Cyclosporine, business, Immunosuppressive Agents, 030215 immunology
Abstract: Introduction Aplastic anemia (AA) is a rare but potentially life-threatening disease that frequently occurs in older patients. Various therapeutic options can be proposed and data regarding the ideal first line treatment of AA in this ageing population remains scarce. Methods We conducted a retrospective nationwide multicenter study in France to examine current treatments for AA patients over 60 years old within a 10-year period (1/1/2007 to 12/31/2016). Our aims were to evaluate efficacy and tolerance of AA treatment, and to analyze predictive factors for response and survival. Patients who were diagnosed with AA by a bone marrow biopsy at the age of 60 or over were included in the study. Results Over the course of a decade, 88 patients (median age 68.5) were identified in 19 centers, with a median follow-up of 32.1 months; 49% were women, the median Charlson comorbidity index was 2 (range 0-6), the median performance status was 1 (range 0-3), 21% had very severe (vSAA) and 36% severe AA. We analyzed 184 treatment lines which comprised ATG-CsA (33%, including 72% with horse ATG), CsA alone (14%), androgen alone (14%), eltrombopag alone (10%), CsA associated with androgen or eltrombopag (9%), and other treatments (20%). First-line treatment was ATG-CsA for half of patients. Comparisons of patients treated in first line with ATG-CsA, CsA or other treatments revealed that patients receiving ATG-CsA were significantly younger (66 years, vs. 71.5 vs. 71.5, respectively, p=0.007), more frequently female (61%, vs. 50% vs. 27%, p=0.02) and had a lower platelet count (8x109/L, vs. 12x109/L vs. 15x109/L, p=0.025). We found no difference with respect to weight, Charlson comorbidity index score, performance status or disease severity between first line treatment regimens. After first-line therapy, 32% of patients achieved a complete response (CR), and 15% a partial response (PR). After the 181 assessable treatment lines, 19% achieved CR and 19% a PR. Median time until best response was 151 days. The overall response rate (ORR) was 62% with ATG-CsA (70% as a first-line treatment), 35% with CsA alone (39% as first-line), 22% with eltrombopag, and 21% with androgen. The ORR in patients over 70 years receiving ATG-CsA (n=16) was 81% (50% achieving a CR). Responses were significantly better in first line and in patients with good performance status, as well as in those that had received ATG-CsA (ORR of 70% after first-line treatment). In a multivariable analysis using ATG-CsA as a baseline, we found that CsA alone (OR 0.35 (0.13;0.96), p=0.042), eltrombopag (OR 0.12 (0.03;0.54), p=0.0057) and androgens (OR 0.17 (0.05;0.58), p=0.0047) were all individually associated with lower response rates. The main complications were infections (grade III/IV, 35% of treatment lines including 9 deaths (5%)), and renal issues (grade-III/IV, 29%). ATG-CsA was associated with significantly more infectious complications (72% vs. 24%, p Conclusion Our study showed a significantly better ORR with ATG-CsA than other regimens for treatment of AA in elderly, with more complications but no more death. Age per se is not a limiting factor for treatment with ATG-CsA: this regimen should be used as first-line treatment in elderly patients if they have a good performance status and low comorbidity index score. Among patients with adverse performance status or comorbidities contra-indicating the use of ATG, CsA alone or in combination may be safely used. Other strategies might be reserved for later courses of treatments. Supportive care may have a great impact on survival in this population. Disclosures Ades: JAZZ: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees; silent pharma: Consultancy; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Peffault De Latour:Pfizer Inc.: Consultancy, Honoraria, Research Funding; Amgen Inc.: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding.
Published: 2019

27. A phase II study of guadecitabine in higher-risk myelodysplastic syndrome and low blast count acute myeloid leukemia after azacitidine failure

Author: Sophie Park, Anne Banos, Cendrine Chaffaut, Cecile Bally, Kamel Laribi, Laurence Legros, Aline Renneville, Pierre Fenaux, Emmanuel Gyan, Eric Wattel, Marie Sebert, Marie-Pierre Gourin, Sylvie Chevret, Claude Preudhomme, Simone Jueliger, Fatiha Chermat, Pierre Peterlin, Olivier Nibourel, Odile Beyne-Rauzy, Lionel Ades, Rosa Sapena, Aspasia Stamatoullas, Luke Bevan, and Laurence Sanhes
Subjects: Male, Risk, medicine.medical_specialty, Azacitidine, Decitabine, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, medicine, Humans, Survival analysis, Aged, business.industry, Myeloid leukemia, Hematology, medicine.disease, Survival Analysis, Leukemia, Leukemia, Myeloid, Acute, Treatment Outcome, Hypomethylating agent, International Prognostic Scoring System, Myelodysplastic Syndromes, Female, business, 030215 immunology, medicine.drug
Abstract: High-risk myelodysplastic syndrome/acute myeloid leukemia patients have a very poor survival after azacitidine failure. Guadecitabine (SGI-110) is a novel subcutaneous hypomethylating agent which results in extended decitabine exposure. This multicenter phase II study evaluated the efficacy and safety of guadecitabine in high-risk myelodysplastic syndrome and low blast count acute myeloid leukemia patients refractory or relapsing after azacitidine. We included 56 patients with a median age of 75 years [Interquartile Range (IQR) 69-76]. Fifty-five patients received at least one cycle of guadecitabine (60 mg/m2/d subcutaneously days 1-5 per 28-day treatment cycles), with a median of 3 cycles (range, 0-27). Eight (14.3%) patients responded, including two complete responses; median response duration was 11.5 months. Having no or few identified somatic mutations was the only factor predicting response (P=0.035). None of the 11 patients with TP53 mutation responded. Median overall survival was 7.1 months, and 17.9 months in responders (3 of whom had overall survival >2 years). In multivariate analysis, IPSS-R (revised International Prognostic Scoring System) score other than very high (P=0.03) primary versus secondary azacitidine failure (P=0.01) and a high rate of demethylation in blood during the first cycle of treatment (P=0.03) were associated with longer survival. Thus, guadecitabine can be effective, sometimes yielding relatively prolonged survival, in a small proportion of high-risk myelodysplastic syndrome/low blast count acute myeloid leukemia patients who failed azacitidine. (Trial registered at clinicaltrials.gov identifier: 02197676).
Published: 2019

28. A randomized phase 3 trial of auto vs. allo transplantation as part of first-line therapy in poor-risk peripheral T-NHL

Author: Martin Wilhelm, Bettina Altmann, Mathieu Leclerc, Laurence de Leval, Ulrich Keller, Arnaud Jaccard, Emmanuel Gyan, Olivier Tournilhac, Peter Reimer, Maike Nickelsen, Martin Dreyling, Jacques-Olivier Bay, Karin Bilger, Bernd Metzner, Andreas Viardot, Laurence Sanhes, Murielle Roussel, Philippe Gaulard, Marita Ziepert, Noel Milpied, Gandhi Damaj, Norbert Schmitz, Friederike Braulke, Walter Lindemann, Eva Maria Wagner-Drouet, Alain Delmer, Bertram Glass, Guillaume Cartron, Thierry Lamy, Krimo Bouabdallah, Viola Poeschel, Frank Kroschinsky, Birte Friedrichs, Lorenz Truemper, David Sibon, Peter Dreger, Andreas Rosenwald, Christian Gisselbrecht, Mathias Haenel, Anne Banos, Gerald Wulf, University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), Georg-August-University [Göttingen], Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Universität Leipzig [Leipzig], Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Limoges, Kliniken Essen-Mitte, University Medical Center [Mainz], Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Centre Hospitalier Saint Jean de Perpignan, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Catholic Hospital = Katholisches Krankenhaus [Hagen], Universität Heidelberg [Heidelberg], Universitätsklinikum Ulm - University Hospital of Ulm, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), CHU Clermont-Ferrand, Helios-Klinikum Berlin-Buch, University Hospital Homburg, Institut d'Hématologie de Basse-Normandie (IHBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, CHU Necker - Enfants Malades [AP-HP], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Institut de Cancérologie de Strasbourg Europe (ICANS), Le CHCB, Centre Hospitalier de la Côte Basque, Hospital of Chemnitz, Klinikum der Universität [München], Klinikum Oldenburg, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Onkologie Lerchenfeld [Hamburg], CHU Estaing [Clermont-Ferrand], Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne (UCA), CIC Clermont Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-Centre de Pharmacologie Clinique, Georg-August-University = Georg-August-Universität Göttingen, Universität Leipzig, Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Julius-Maximilians-Universität Würzburg (JMU), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Universität Heidelberg [Heidelberg] = Heidelberg University, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier de la Côte Basque (CHCB), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Herrada, Anthony
Subjects: 0301 basic medicine, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Vincristine, medicine.medical_specialty, Allogeneic transplantation, Immunology, CHOP, Biochemistry, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, International Prognostic Index, Autologous stem-cell transplantation, immune system diseases, Internal medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Anaplastic large-cell lymphoma, Etoposide, Lymphoid Neoplasia, business.industry, Lymphoma, T-Cell, Peripheral, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cell Biology, Hematology, medicine.disease, 3. Good health, Transplantation, 030104 developmental biology, surgical procedures, operative, business, human activities, 030215 immunology, medicine.drug
Abstract: Standard first-line therapy for younger patients with peripheral T-cell lymphoma consists of six courses of CHOP or CHOEP consolidated by high-dose therapy and autologous stem cell transplantation (AutoSCT). We hypothesized that consolidative allogeneic transplantation (AlloSCT) could improve outcome. 104 patients with nodal peripheral T-cell lymphoma except ALK+ ALCL, 18 to 60 years of age, all stages and IPI scores except stage 1 and aaIPI 0, were randomized to receive 4 x CHOEP and 1 x DHAP followed by high-dose therapy and AutoSCT or myeloablative conditioning and AlloSCT. The primary endpoint was event-free survival (EFS) at three years. After a median follow-up of 42 months, 3-year EFS of patients undergoing AlloSCT was 43% (95% confidence interval [CI]: 29%; 57%) as compared to 38% (95% CI: 25%; 52%) after AutoSCT. Overall survival at 3 years was 57% (95% CI: 43%; 71%) versus 70% (95% CI: 57%; 82%) after AlloSCT or AutoSCT, without significant differences between treatment arms. None of 21 responding patients proceeding to AlloSCT as opposed to 13 of 36 patients (36%) proceeding to AutoSCT relapsed. Eight of 26 patients (31%) and none of 41 patients died due to transplant-related toxicity after allogeneic and autologous transplantation, respectively. In younger patients with T-cell lymphoma standard chemotherapy consolidated by autologous or allogeneic transplantation results in comparable survival. The strong graft-versus-lymphoma effect after AlloSCT was counterbalanced by transplant-related mortality. CHO(E)P followed by AutoSCT remains the preferred treatment option for transplant-eligible patients. AlloSCT is the treatment of choice for relapsing patients also after AutoSCT.
Published: 2021

29. Venous thromboembolism during systemic inflammatory and autoimmune diseases associated with myelodysplastic syndromes, chronic myelomonocytic leukaemia and myelodysplastic/myeloproliferative neoplasms: a French multicentre retrospective case-control study

Author: Marie Péan de Ponfilly-Sotier, Vincent Jachiet, Ygal Benhamou, Constance Lahuna, Benoit De Renzis, Diane Kottler, Laurent Voillat, Sophie Dimicoli-Salazar, Anne Banos, Marie-Paule Chauveheid, Jean-François Alexandra, Eric Grignano, François Liferman, Mathilde Laborde, Jonathan Broner, Marc Michel, Olivier Lambotte, Kamel Laribi, Marie-Dominique Venon, Bertrand Dussol, Nihal Martis, Sylvain Thepot, Sophie Park, David Couret, Marielle Roux-Sauvat, Louis Terriou, Eric Hachulla, Cécile Bally, Joris Galland, Jean-Sébastien Allain, Anne Parcelier, Pierre Peterlin, Judith Cohen-Bittan, Alexis Regent, Felix Ackermann, Julien Le Guen, Caroline Algrin, Pierre Charles, Etienne Daguindau, Xavier Puechal, Bertrand Dunogue, Claire Blanchard-Delaunay, Odile Beyne-Rauzy, Vincent Grobost, Jean Schmidt, Thomas Le Gallou, Georgeta Dubos-Lascu, Anne Sonet, Guillaume Denis, Frédérique Roy-Peaud, Pierre Fenaux, Lionel Adès, Olivier Fain, Arsène Mekinian, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), and Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: MESH: Humans, [SDV]Life Sciences [q-bio], Immunology, MESH: Retrospective Studies, Leukemia, Myelomonocytic, Chronic, Venous Thromboembolism, MESH: Case-Control Studies, MESH: Venous Thromboembolism, Autoimmune Diseases, Rheumatology, MESH: Autoimmune Diseases, Case-Control Studies, Myelodysplastic Syndromes, Immunology and Allergy, Humans, MESH: Leukemia, Myelomonocytic, Chronic, MESH: Myelodysplastic Syndromes, Retrospective Studies
Abstract: International audience; Objectives: Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML) are associated with systemic inflammatory and autoimmune diseases (SIADs) in 10-30% of cases. The aims of this study were (i) to evaluate the prevalence of venous thromboembolism VTE in patients presenting with both MDS/CMML and SIADs, (ii) to describe risk factors associated with thrombosis, and (iii) to analyse the impact of VTE on overall survival and transformation to acute myeloid leukaemia in comparison to patients with MDS/CMML-associated SIADs without VTE.Methods: This retrospective multicentre case-control study was conducted among patients with MDS/CMML and dysimmune disorders and featured in the French retrospective database of the French Network of Dysimmune Disorders Associated with Hemopathies (MINHEMON), diagnosed with MDS/CMML and dysimmune disorders.Results: During a median follow-up of 16 months (5-48) VTE occurred in 35 patients (21.6 %) whereas 127 patients did not. Among those with VTE, 8 patients (22.9%) experienced two or more VTE. Common prothrombotic risk factors were not significantly different in patients with or without VTE. CMML was more frequent in patients without VTE (37 % vs. 14.3%, p=0.01), whereas myelodysplasic/myeloproliferative neoplasm (MDS/MPN) was higher in VTE patients (20 % vs. 5.5 %, p=0.01). In a multivariate analysis, only MDS/CMML progression at the time of VTE (odds ratio 28.82, 95 % CI (5.52-530.70) was significantly associated with VTE. When treated with an anticoagulation therapy, bleeding occurred in 19.4% of cases (6/31). Overall survival was not significantly different between patients with and without VTE (p=0.68). Leukaemia-free survival between groups was not significantly different (p=0.83).Conclusions: VTE is a common complication in MDS/CMML-associated SIADSs with an increased risk of bleeding when treated by anticoagulants. In the MDS/CMML subgroup, SIADS flares and MDS/CMML progression seem to be prothrombotic risk factors.
Published: 2021

30. Molecular classification and prognosis in younger adults with acute myeloid leukemia and intermediate-risk cytogenetics treated or not by gemtuzumab ozogamycin: Final results of the GOELAMS/FILO acute myeloid leukemia 2006-intermediate-risk trial

Author: Norbert Ifrah, Hacene Zerazhi, Pierre-Yves Dumas, Norbert Vey, Isabelle Luquet, Denis Caillot, Marie-Christine Béné, Célestine Simand, Marie-Pierre Ledoux, Véronique Dorvaux, Yosr Hicheri, Anne Banos, Maria Pilar Gallego Hernanz, Chantal Himberlin, Odile Blanchet, Eric Delabesse, Catherine Humbrecht, Pascal Turlure, Arnaud Pigneux, Eric Jourdan, Jacques Delaunay, Didier Bouscary, Emmanuelle Tavernier, Christian Recher, Gaelle Guillerm, Mathilde Hunault-Berger, Romain Guieze, Martin Carre, Anne Bouvier, Jean-Pierre Marolleau, Claude Eric Bulabois, Pascale Cornillet-Lefebvre, Mario Ojeda-Uribe, Marc Bernard, Magda Alexis, Jean-François Hamel, Etienne Daguindau, Pierre Peterlin, Gabrielle Roth Guepin, Emmanuel Gyan, Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital privé du Confluent [Nantes], Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Bordeaux, Service d'Hématologie Clinique et Thérapie Cellulaire, F-33000 Bordeaux, France., Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de Strasbourg Europe (ICANS), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire [Grenoble] (CHU), Service d'Hématologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne (UCA), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Reims (CHU Reims), Fédérations hospitalo-universitaires Grand Ouest Acute Leukemia [Angers] (FHU GOAL), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service des maladies du sang [Angers], CHU Pontchaillou [Rennes], Département d'Hématologie [CHU Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier de la Côte Basque (CHCB), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre National de la Recherche Scientifique (CNRS)-Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT)-Université de Tours (UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional d'Orléans (CHRO), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre Hospitalier Henri Duffaut (Avignon), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Ressources Biologiques [CHU Angers], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Service d'Hématologie Biologique [Hôpital Robert Debré, Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Oncology, Adult, Male, Risk, medicine.medical_specialty, NPM1, Adolescent, medicine.medical_treatment, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, Phases of clinical research, Gene mutation, Disease-Free Survival, Cytogenetics, Young Adult, Internal medicine, hemic and lymphatic diseases, CEBPA, Medicine, Cluster Analysis, Humans, Chemotherapy, business.industry, Gene Expression Regulation, Leukemic, Gene Expression Profiling, Remission Induction, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, Hematology, General Medicine, Middle Aged, Prognosis, Gemtuzumab, Transplantation, Leukemia, Myeloid, Acute, Karyotyping, Cytogenetic Analysis, Mutation, Female, business
Abstract: International audience; In this randomized phase 3 study, the FILO group tested whether the addition of 6 mg/m(2) of gemtuzumab ozogamycin (GO) to standard chemotherapy could improve outcome of younger patients with de novo acute myeloid leukemia (AML) and intermediate-risk cytogenetics. GO arm was prematurely closed after 254 inclusions because of toxicity. A similar complete remission rate was observed in both arms. Neither event-free survival nor overall survival were improved by GO in younger AML patients (
Published: 2021

31. Data from French named patient program of quizartinib in relapsed/refractory acute myeloid leukemia

Author: Anne Banos, Stefan Wickenhauser, Fabrice Larosa, Filo, R. Redjoul, Pierre-Yves Dumas, Nolwenn Lucas, Jamile Frayfer, Martin Carre, M. Alexis, M. Elassy, Arnaud Pigneux, Emmanuel Raffoux, Pierre Peterlin, Marie-Virginie Larcher, N. Maillard, Christian Recher, J. Michel, J. B. Mear, M. Detrait, V. Morel, Sylvain Chantepie, Mario Ojeda-Uribe, Y. Desbrosses, S. Fodil, Celia Salanoubat, Hervé Dombret, Thomas Cluzeau, C. Mediavilla, Sarah Bertoli, Driss Chaoui, Mathilde Hunault-Berger, and V. Vidal
Subjects: Oncology, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Text mining, Internal medicine, medicine, Overall survival, Humans, Benzothiazoles, Quizartinib, Chemotherapy, business.industry, Phenylurea Compounds, Hazard ratio, Myeloid leukemia, Hematology, Leukemia, Myeloid, Acute, chemistry, fms-Like Tyrosine Kinase 3, 030220 oncology & carcinogenesis, Relapsed refractory, business, 030215 immunology, Chemotherapy group
Abstract: Quizartinib improved outcome compared to chemotherapy in the QuANTUM-R study (median overall survival (OS): 6.2 months for quizartinib vs. 4.7 in the chemotherapy group; hazard ratio 0.76, p = 0.02...
Published: 2021

32. Very Long Term Follow up a Phase II Study of Post-Remission Subcutaneous (SC) Azacitidine (AZA) in Patients with AML Post-MDS or Higher-Risk (HR) MDS

Author: Lionel Ades, Krimo Bouabdallah, Xavier Thomas, Chantal Himberlin, Denis Caillot, Emmanuel Raffoux, Amina Cherait, Agnès Guerci, Hervé Dombret, Fatiha Chermat, Arnaud Pigneux, Sylvie Chevret, Pierre Fenaux, Anne Banos, Claude Gardin, Thorsten Braun, Jean Pierre Marolleau, Norbert Vey, Cécile Pautas, Anne Laure Taksin, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Avicenne [AP-HP], Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), CHU Bordeaux [Bordeaux], CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire de Nancy (CHU Nancy), CHU Amiens-Picardie, CHU Henri Mondor, Le CHCB, Centre Hospitalier de la Côte Basque, Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier de Versailles André Mignot (CHV), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hématopoïèse normale et pathologique : émergence, environnement et recherche translationnelle [Paris] ((UMR_S1131 / U1131)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Recherche clinique appliquée à l'hématologie ((EA_3518)), Université Paris Diderot - Paris 7 (UPD7), and DESSAIVRE, Louise
Subjects: Oncology, medicine.medical_specialty, Long term follow up, business.industry, [SDV]Life Sciences [q-bio], Immunology, Azacitidine, Phases of clinical research, Cell Biology, Hematology, Biochemistry, [SDV] Life Sciences [q-bio], Internal medicine, medicine, In patient, business, ComputingMilieux_MISCELLANEOUS, medicine.drug
Abstract: Background: Results of the phase III QUAZAR trial suggest that post-remission treatment with an oral form (CC-486) of azacitidine (AZA) can prolong CR duration and overall survival(OS) in AML patients reaching at least PR with intensive chemotherapy (IC) (Wei et al, ASH 2019). Maintenance treatment with subcutaneous (SC) AZA was recently shown to improve DFS in elderly AML (Huls et al, Blood 2019, a study that also included 10% MDS). We report very long term results of a study evaluating SC AZA as post-remission treatment in patients with AML post-MDS or high-risk MDS (HR-MDS) who achieved at least PR after IC, a population known to have short responses with IC. Methods: Inclusion criteria were (1) HR-MDS according to IPSS, or AML after a documented phase of MDS(2) who entered CR, CRi or PR after IC with anthracycline and AraC within 28 days of inclusion (3) ECOG Results: From July 2006 to June 2009, 51 pts (M:31/F:20) were included. The 46 evaluable pts had achieved CR (n=28), CRi (n=11), and PR (n=7) before study entry. Median age was 66y (range 55-78). Diagnosis at IC onset was MDS (n=13) and AML (n=33), IPSS cytogenetics was normal (n= 28), intermediate (n=10), high (n= 6), and failed (n=2). Median time from diagnosis of MDS to IC was 8 months (range 0.5-101). Median number of AZA maintenance cycles was 7.5 (1-76) in CR pts (>23 cycles in 5 of them) and 4.5 (1-24) in CRi or PR pts (> 23 cycles in 1). Two patients were allografted and censored at allo SCT. Median follow-up was 16.5 months As of May 2020 (cut off date of analysis) median DFS and OS from response were 6.9 m and 16.9 m, respectively (figure). In CR patients, median and 18 months OS were 18.9 months and 58%, versus 12.8 months and 50% in CRi-PR patients (p=0.33) All non allografted patients eventually relapsed. 7 had a response duration >18 months (6 CR patients: 22, 23, 25, 36, 40, and 84 months; 1 CRi patient: 24 months) OS from inclusion was >3 years in 7 patients (CR pts: 150, 126,74, 51, 50,40 months; CRi pt:58 months), in addition to the 2 allografted pts who remained alive in CR at 156+ and 159+ months No baseline factor including cytogenetics, diagnosis at IC onset (MDS vs AML), % bone marrow blasts, age or time from MDS diagnosis to treatment, significantly predicted DFS or OS. AZA dosing in CR patients was escalated in 9 pts to 75mg/m2/d due to good tolerance but had to be reduced in 6 pts, due to GI toxicity (n=1) and cytopenias (n=5). During SC AZA maintenance, 2/28 CR pts developed febrile neutropenia, compared to 4/18 pts in CRi or PR (including 1 fatal case). In the 22 AML post MDS pts who reached CR, DFS and OS were similar to those observed in 46 AML post AML pts included in a previous ALFA study where pts in CR after IC received DNR/IDA-AraC post-remission therapy (Gardin, Blood 2007). Conclusion: In the very long term analysis of this trial in AML post MDS and HR-MDS treated with induction intensive chemotherapy, post-remission therapy with SC AZA alone was associated with a median DFS and OS of 6.9 and 16.9 months, respectively, with some prolonged response. Results appeared similar to those we had reported with intensive consolidation chemotherapy, but using an ambulatory treatment with limited myelosuppression. Figure Disclosures Braun: Daiichy-Sankyo: Honoraria; Servier: Research Funding. Bouabdallah:Takeda: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria. Ades:Celgene/BMS: Research Funding; novartis: Research Funding; takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; jazz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding. Fenaux:Abbvie: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Jazz: Honoraria, Research Funding.
Published: 2020

33. Maintenance of Long-Term Undetectable Minimal Residual Disease after Combination of Ibrutinib with Abbreviated Chemotherapy in the Icll-07 Filo Trial

Author: Anne Banos, Vincent Levy, Magali Le Garff-Tavernier, Veronique Leblond, Sophie de Guibert, Valérie Rouille, Loic Ysebaert, Philippe Carassou, Bruno Villemagne, Kamel Laribi, Alain Delmer, Frederique Orsini, Beatrice Mahe, Michel Ticchioni, Gilles Salles, Marie-Sarah Dilhuydy, Thérèse Aurran, Carmen Aanaei, Florence Nguyen-Khac, Brigitte Pegourie, Rémi Letestu, Fabien Subtil, Luc Mathieu Fornecker, Caroline Dartigeas, Jean Pierre Vilque, Cécile Tomowiak, Guillaume Cartron, Florence Cymbalista, Margot Truchan, Anne-Sophie Michallet, Christelle Portois, Pierre Feugier, Olivier Tournilhac, Stéphane Leprêtre, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), and CHADEYRON, DOMINIQUE
Subjects: Oncology, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.medical_specialty, Cyclophosphamide, medicine.medical_treatment, Immunology, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Obinutuzumab, Internal medicine, medicine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Chemotherapy, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cell Biology, Hematology, Chemotherapy regimen, Minimal residual disease, 3. Good health, Fludarabine, chemistry, Ibrutinib, Rituximab, business, 030215 immunology, medicine.drug
Abstract: Introduction In previously untreated, medically fit patients with chronic lymphocytic leukaemia (CLL) and no 17p deletion, there is current research interest in improving survival outcomes and potentially sparing some patients from the standard 6 cycles of fludarabine, cyclophosphamide and rituximab (FCR). The phase II ICLL-07 (NCT02666898) trial, conducted by the French Innovative Leukemia Organization (FILO), aimed to explore the efficacy of obinutuzumab and ibrutinib treatment induction for 9 months, followed by a minimal residual disease (MRD)-driven strategy. Methods Following assessment at Month 9, patients in complete response (CR) with bone marrow (BM) MRD ResultsBetween 10/2015 and 05/2017, 135 patients were enrolled. At Month 9, only 8% of patients reached CR with BM MRD Conclusion These findings from the ICLL-07 trial demonstrated that, in previously untreated, medically fit patients with CLL and no 17p deletion, treatment induction with obinutuzumab and ibrutinib followed by an MRD-driven strategy yielded a high rate of CR with BM and PB MRD Disclosures Salles: Roche, Janssen, Gilead, Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Amgen: Honoraria, Other: Educational events. Leblond:Gilead: Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Astra Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Cartron:Roche, Celgene: Consultancy; Sanofi, Gilead, Janssen, Roche, Celgene: Honoraria. Cymbalista:Sunesis: Research Funding; Roche: Research Funding; Janssen: Honoraria; Abbvie: Honoraria; AstraZeneca: Honoraria; Gilead: Honoraria. Le Garff-Tavernier:Alexion: Consultancy, Honoraria. Letestu:Alexion: Membership on an entity's Board of Directors or advisory committees, Other: speaker fee, expert contracts; Roche: Membership on an entity's Board of Directors or advisory committees, Other: speaker fee, expert contracts; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: speaker fee, expert contracts; Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: speaker fee, expert contracts. Feugier:janssen: Honoraria, Research Funding, Speakers Bureau; gilead: Honoraria, Research Funding, Speakers Bureau; abbvie: Honoraria, Research Funding, Speakers Bureau; roche: Honoraria, Research Funding, Speakers Bureau.
Published: 2019

34. Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma

Author: Anne Banos, Michel Attal, Salomon Manier, Christine Chen, Jin Lu, Javier de la Rubia, Andrew Belch, Michele Cavo, Angela Dispenzieri, Mourad Tiab, John Catalano, Guang Chen, Lugui Qiu, Aurore Perrot, Je-Jung Lee, Katja Weisel, Hervé Avet-Loiseau, Vanessa Houck, Philippe Moreau, Murielle Roussel, Thierry Facon, Nizar J. Bahlis, Heinz Ludwig, Kenneth C. Anderson, Antonello Pinto, Catarina Geraldes, Xavier Leleu, Bertrand Arnulf, Annette Ervin-Haynes, Albert Oriol, Lotfi Benboubker, Meletios A. Dimopoulos, Daniel Binder, Eileen M Boyle, Cyrille Hulin, Darrell White, Jamie D. Cavenagh, Michel Delforge, Mohamad Mohty, Facon, Thierry, Dimopoulos, Meletios A, Dispenzieri, Angela, Catalano, John V, Belch, Andrew, Cavo, Michele, Pinto, Antonello, Weisel, Katja, Ludwig, Heinz, Bahlis, Nizar J, Banos, Anne, Tiab, Mourad, Delforge, Michel, Cavenagh, Jamie D, Geraldes, Catarina, Lee, Je-Jung, Chen, Christine, Oriol, Albert, De La Rubia, Javier, White, Darell, Binder, Daniel, Jin, Lu, Anderson, Kenneth C, Moreau, Philippe, Attal, Michel, Perrot, Aurore, Arnulf, Bertrand, Qiu, Lugui, Roussel, Murielle, Boyle, Eileen, Manier, Salomon, Mohty, Mohamad, Avet-Loiseau, Herve, Leleu, Xavier, Ervin-Haynes, Annette, Chen, Guang, Houck, Vanessa, Benboubker, Lotfi, and Hulin, Cyrille
Subjects: Melphalan, medicine.medical_specialty, Clinical Trials and Observations, Immunology, Urology, Antineoplastic Agents, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, newly diagnosed multiple myeloma, medicine, Clinical endpoint, Humans, Progression-free survival, Survival analysis, Lenalidomide, business.industry, Hazard ratio, Cell Biology, Hematology, Survival Analysis, Progression-Free Survival, Surgery, Thalidomide, Transplantation, Treatment Outcome, 030220 oncology & carcinogenesis, Multiple Myeloma, business, 030215 immunology, medicine.drug
Abstract: This FIRST trial final analysis examined survival outcomes in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) treated with lenalidomide and low-dose dexamethasone until disease progression (Rd continuous), Rd for 72 weeks (18 cycles; Rd18), or melphalan, prednisone, and thalidomide (MPT; 72 weeks). The primary endpoint was progression-free survival (PFS; primary comparison: Rd continuous vs MPT). Overall survival (OS) was a key secondary endpoint (final analysis prespecified ≥60 months' follow-up). Patients were randomized to Rd continuous (n = 535), Rd18 (n = 541), or MPT (n = 547). At a median follow-up of 67 months, PFS was significantly longer with Rd continuous vs MPT (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.59-0.79; P < .00001) and was similarly extended vs Rd18. Median OS was 10 months longer with Rd continuous vs MPT (59.1 vs 49.1 months; HR, 0.78; 95% CI, 0.67-0.92; P = .0023), and similar with Rd18 (62.3 months). In patients achieving complete or very good partial responses, Rd continuous had an ≈30-month longer median time to next treatment vs Rd18 (69.5 vs 39.9 months). Over half of all patients who received second-line treatment were given a bortezomib-based therapy. Second-line outcomes were improved in patients receiving bortezomib after Rd continuous and Rd18 vs after MPT. No new safety concerns, including risk for secondary malignancies, were observed. Treatment with Rd continuous significantly improved survival outcomes vs MPT, supporting Rd continuous as a standard of care for patients with transplant-ineligible NDMM. This trial was registered at www.clinicaltrials.gov as #NCT00689936 and EudraCT as 2007-004823-39.
Published: 2018

35. A Phase II Study of the Efficacy and Tolerance of Azacytidine (AZA) in Steroid Dependent/Refractory Systemic Autoimmune and Inflammatory Disorders (SAID) Associated with MDS or CMML (GFM- AZA-SAID -trial)

Author: Vincent Jachiet, Fatiha Chermat, Stefan Wickenhauser, Louis Terriou, Marie-Pierre Gourin, Thibault Comont, Arsène Mekinian, Alexandre Thibault Jacques Maria, Laurent Pascal, Pierre Peterlin, Odile bayne Rouzy, Laurent Voillat, Karine Lemaire, Pierre Fenaux, Kristell Desseaux, Sylvie Chevret, Eric Durot, Norbert Vey, Lionel Ades, Olivier Fain, Anne Vekhoff, Sophie Dimicoli Salazar, Shanti Ame, Maud d'Aveni, Benoit de Renzis, Anne Banos, Lin-Pierre Zhao, and Rose Rose
Subjects: Steroid dependency, Refractory, business.industry, Immunology, Phases of clinical research, Medicine, Cell Biology, Hematology, Pharmacology, business, Biochemistry
Abstract: Background: Systemic autoimmune and inflammatory diseases (SAIDs) occur in 10-15% of MDS or CMML patients. They are often severe, difficult to treat and steroid resistant/dependent disorders. In a retrospective report of 22 patients with steroid-dependent MDS/CMML associated SAID, we observed promising results with azacytidine (AZA) on the SAID component (Fraison et al, Leuk Res, 2016). In this prospective French nationwide trial, we aimed at confirming this effect prospectively. Patients and Methods: This open-label, single-arm multicenter, phase II study included MDS/CMML patients with IPSS/CPSS int 2 or high, or lower IPSS/CPSS but with significant cytopenias, especially ESA resistant anemia (or, for CMML, proliferative features) and SAID with steroid dependence and/or resistance. The primary endpoint was response rate (RR, including CR and PR) of SAID after 6 cycles of AZA. Secondary endpoints included RRof SAID after 3 cycles of AZA, response of MDS, time to MDS progression (including to AML), overall survival (OS) and safety. AZA was used at 75 mg/m²/d x 7 days, every 4 weeks for a minimum of 6 cycles (unless overt disease progression occurred before). At the onset of AZA, prednisone (PRED) was administered at 1 mg/kg during 1 month and then decreased progressively over 6 months. Results: 30 patients were included between July 2017 and June 2020 , 29 of whom received AZA and were considered evaluable: median age 72 [range 68-78], 69% males; WHO: MDS ML (n=11; 41%), CMML (n=11, 41%), MDS-RS (n=2, 7%), EB-1 (n=1) and EB-2 (n=1), unclassified (n=3); IPSS-R : good (n=15, 54%), very good (n=3; 11%, each), intermediate (n=7; 25%) and very poor profile (n=3; 11%) (all CMML had WBC 19 patients (65.5%, IC95% [45.7.82.1]) obtained a SAID response after 6 cycles (including 8 CR and 11 PR), while 17 (58.6% (IC95% [38.9; 76.5]) patients achieved an IWG 2006 hematological response (7 CR, 9 SD with HI and 1 marrow CR). All the 13 patients who received 12 cycles of AZA achieved SAID CR or PR at 12 months, and 10 of them had a hematological response (6 CR, 1PR, 2 HI, 1 marrow CR). The SAID response rate at 12 month was at 72.4% (IC95% : [51.3;85.6]). SAIDs complete/partial response occurred in 3/9 (33%) UBAI-positive versus 8/19 (42%) non-mutated cases. No significant prognostic factor of SAID response after 6 cycles, including sex, age, WHO classification, IPSS-R, UBA1 and TET-2 mutation status was found. With a median follow-up of 18.5 months [11.8; 24.3], 9 (31%) patients had died, with a 1-year OS of 82.3% (IC95% [69.4; 97.7]. At least one SAE occurred in 23 patients, with a median of 2 events/patient [1.5; 5.5]. Death was due to infection (n=5, two of them in patients with good IPSS-R, but severe steroid dependent SAID), MDS progression (n=2), or unrelated causes (n=2). Conclusion We confirmed prospectively an effect of AZA on the autoimmune/inflammatory component in two thirds of MDS/CMML patients with steroid dependent / refractory concomitant systemic autoimmune/inflammatory disease. No significant difference in AZA response was noted between UBA1 mutated and unmutated MDS patients. The adverse events and mortality rates, often from infectious origin, appear to be those expected in such an MDS population, potentially worsened by the associated SAID and background of immunosuppressive treatment (especially steroids) Disclosures Terriou: Alexion, AstraZeneca Rare Disease: Consultancy, Membership on an entity's Board of Directors or advisory committees. Vey: Amgen: Honoraria; BMS: Honoraria; BIOKINESIS: Consultancy, Research Funding; NOVARTIS: Consultancy, Honoraria, Research Funding; SERVIER: Consultancy; JAZZ PHARMACEUTICALS: Honoraria; JANSSEN: Consultancy. Ades: ABBVIE: Honoraria; TAKEDA: Honoraria; CELGENE/BMS: Honoraria; NOVARTIS: Honoraria; JAZZ: Honoraria, Research Funding; CELGENE: Research Funding. Fenaux: Abbvie: Honoraria, Research Funding; JAZZ: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Celgene/BMS: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Syros Pharmaceuticals: Honoraria.
Published: 2021

36. Salvage Therapy with Brentuximab-Vedotin and Bendamustine for Patients with Relapsed/Refractory T Cell Lymphoma. a Multicenter and Retrospective Study

Author: Philippe Gaulard, David Sibon, Ludovic Fouillet, Kossi Agbetiafa, Anne Banos, Christophe Bonnet, Krimo Bouabdallah, Loïc Chartier, Marie Parrens, Marwa Hammami, Eric Durot, Kamel Laribi, Gandhi Damaj, Mathieu Bellal, Noel-Jean Milpied, Sandy Amorim, Ronan Le Calloch, Fontanet Bijou, Margot Robles, Marlene Ochmann, Thomas Cluzeau, Olivier Tournilhac, Charles Herbaux, Nicolas Daguindau, Adrien Chauchet, Raphaëlle Aubrais, Jean Marc Schiano De Colella, and Pauline Brice
Subjects: Oncology, Bendamustine, medicine.medical_specialty, business.industry, Immunology, Salvage therapy, Retrospective cohort study, Cell Biology, Hematology, medicine.disease, Biochemistry, Internal medicine, Relapsed refractory, medicine, T-cell lymphoma, business, Brentuximab vedotin, medicine.drug
Abstract: Methods : This multicentric retrospective study aimed to evaluate the efficacy and the safety of the combination of BBV in patients with non-cutaneous R/R PTCL among 21 LYSA centers in France and Belgium. The primary objective was to evaluate the best overall response rate (ORR) (complete response (CR) and partial response (PR)). Secondary objectives were progression free survival (PFS), overall survival (OS), duration of response (DoR), impact of transplantation on outcome, and safety. Patients treated between January 2013 and October 2020 were reviewed and all the data were collected through an electronic questionnaire sent to all the physicians. Results : Eighty two patients with R/R PTCL (40 angioimmunoblastic lymphoma (AITL), 2 T-cell lymphoma with TFH phenotype ,13 PTCL not otherwise specified (PTCL NOS), 5 Alk+ anaplastic large cell lymphoma (ALCL), 17 Alk- ALCL, , 1 Extranodal NK-/T-cell lymphoma, 3 Enteropathy-associated T-cell lymphoma (EATL), 1 subcutaneous panniculitis) were included. Median age at beginning of BBV was 60 years, most of patients were male (61%), had advanced stage (88%) and an IPI ≥ 2 (79%). Half of patients were refractory to their last treatment. Median number of prior regimens was 1 (range 1 to 6). The best ORR was 71%, with 51% of patients in CR. In multivariable analysis, only the relapse status after the last regimen (relapse vs refractory) was associated with ORR, relapsed patients having a better ORR (83% vs 57% in refractory patients, p=.014, OR=3.70 (95%CI:1.3-10.5)). Median DoR was 15.4 months in patients with CR but differed significantly whether patients were transplanted or not (Not reached vs 8.4 months, p=.0055). Twenty-two patients (30% of patients ≤ 70 years of age) were transplanted (6 autologous and 16 allogenic). With a median follow-up of 9 months, the median PFS and OS were 8.3 and 26.3 months respectively. In multivariable analysis, only 2 factors had a significant impact on PFS and OS: best response (CR/PR vs SD/PD with a median PFS of 17.4 vs 1.9 months, p Fifty-nine percent of patients experienced a grade 3 to 4 adverse event which was mainly hematologic toxicity. Treatment had to be stopped in 11% of patients. Conclusion: To the best of our knowledge, this is the first study reporting on the combination of BBV in the treatment of R/R PTCL in such a large cohort. The results are very encouraging with a high response rate, long DoR in responding patients and a very good outcome. Furthermore, patients in CR who are eligible for transplant have the best outcome, making this combination a good candidate as salvage therapy before transplant consolidation in these high-risk lymphomas with limited treatment options. Figure 1 Figure 1. Disclosures Bouabdallah: Kite/Gilead: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Roche: Consultancy, Honoraria. Herbaux: Takeda: Honoraria, Research Funding; Janssen: Honoraria; Roche: Honoraria; Abbvie: Honoraria, Research Funding. Brice: MSD: Research Funding; Amgen: Other: Travel/accommodations/expenses; Roche: Other: Travel/accommodations/expenses; Takeda: Research Funding. Sibon: Abbvie: Consultancy; Janssen: Consultancy; Roche: Consultancy; iQone: Consultancy; Takeda: Consultancy. Laribi: AstraZeneca: Other: Personal Fees; AbbVie: Other: Personal Fees, Research Funding; IQONE: Other: Personal Fees; Astellas Phama, Inc.: Other: Personal Fees; BeiGene: Other: Personal Fees; Takeda: Other: Personal Fees, Research Funding; Novartis: Other: Personal Fees, Research Funding; Le Mans Hospital: Research Funding; Jansen: Research Funding. Damaj: roche: Consultancy, Honoraria; takeda: Consultancy, Honoraria. OffLabel Disclosure: Brentuximab Vedotin and Bendamustine
Published: 2021

37. SY-1425, a Potent and Selective RARα Agonist, in Combination with Azacitidine Demonstrates a High Complete Response Rate and a Rapid Onset of Response in RARA-Positive Newly Diagnosed Unfit Acute Myeloid Leukemia

Author: Philippe Rousselot, Michael R. Savona, Qing Kang-Fortner, Don Park, Li Zhou, David A. Rizzieri, Carlos E. Vigil, Pierre Fenaux, Eytan M. Stein, David A. Roth, Thomas Cluzeau, Anne Banos, Angela Volkert, Rachel J. Cook, Michael J. Kelly, Thorsten Braun, Jane L. Liesveld, and Stéphane de Botton
Subjects: Agonist, business.industry, medicine.drug_class, Immunology, Azacitidine, Myeloid leukemia, Cell Biology, Hematology, Newly diagnosed, Biochemistry, Rapid onset, Cancer research, Medicine, business, Complete response, medicine.drug
Abstract: Introduction: A novel genomically defined subset of non-APL AML patients (pts) with an actionable target characterized by overexpression of RARA has been identified (McKeown, Cancer Discovery 2017). RARA-positive (RARA+) pts can be detected by a novel blood-based biomarker test that predicts sensitivity to SY-1425, an oral potent and selective RARα agonist (Vigil, ESH 2017). Approximately 30% of newly diagnosed (ND) unfit AML pts are RARA+ (de Botton, ESH 2019), and recent data demonstrates RARA+ AML is correlated with venetoclax resistance, which may suggest a new poor prognostic risk (Fiore, ASH 2020). Preclinical synergy of SY-1425 with azacitidine (aza) supported clinical development of the combination (McKeown, Haematologica 2018), which is currently being evaluated in RARA+ ND unfit AML (NCT02807558). Early data of SY-1425 + aza demonstrated high response rates and a rapid onset of responses in the RARA+ ND unfit AML cohort (Cook, ASH 2018; de Botton, ESH 2019). Updated data for the fully enrolled cohort are presented here. Methods: Both RARA+ and RARA-negative (RARA-) ND unfit AML pts were enrolled, and all pts received aza at 75 mg/m2 IV/SC daily on days 1-7 followed by SY-1425 at 6 mg/m2/day PO in divided doses twice daily on days 8-28 of each 28-day cycle. The primary objective was characterization of activity by the overall response rate (ORR) per IWG. Analyses of the composite complete response rate, time to response, comparison of responses across RARA+ and RARA- cohorts, transfusion independence, and safety were also included. Results: A total of 51 pts were treated, 22 RARA+ and 29 RARA-, with data available through 27 May 2020 reported. Baseline characteristics included 32 (63%) male; median age 76 (60-91); 17 (33%) poor and 33 (65%) intermediate cytogenetic risk; 29 (57%) de novo and 22 (43%) secondary AML; and 33 (65%) with marrow blasts > 30%. Time on treatment was up to 18.2 months, with discontinuation of treatment primarily due to AE (33%), the majority being not treatment-related, and disease progression (22%). Among 18 response-evaluable RARA+ pts, analysis for best response showed an ORR of 67% (12/18), with complete responses in 61% (11/18; 9 CR, 2 CRi, 0 CRh) and MLFS in 6% (1 pt). CRs showed a high rate (89%, 8/9) of complete molecular or cytogenetic remissions (3 molecular, 5 cytogenetic). Median time to initial complete response was rapid at 1.2 months. Transfusion independence (TI) was achieved in 13 (72%) of 18 TI evaluable pts, including conversion to TI in all 6 (100%) who were transfusion dependent at baseline. Of the 28 response-evaluable RARA- pts, the ORR and complete response rate were lower and time to initial response was longer relative to RARA+ pts. ORR was 39%, with complete responses in 29% (8/28; 6 CR, 2 CRi, 0 CRh). Median time to initial complete response was 2.9 months. The AE profile of the combination is consistent with that previously reported for single-agent SY-1425 or aza in AML. Most common AEs (all grades/causality) included decreased appetite (41%; 21/51 pts), hypertriglyceridemia (41%), nausea (39%), constipation (39%), fatigue (35%), peripheral edema (35%), pyrexia (33%) and febrile neutropenia (33%). Hematologic AEs ≥ grade 3 included febrile neutropenia (33%), thrombocytopenia (24%), anemia (20%) and neutropenia (16%). The majority of non-hematologic AEs were low grade. The most frequent SAEs included febrile neutropenia (27%), pyrexia (12%), pneumonia (12%), and sepsis (10%). Conclusion: SY-1425 + aza was generally well-tolerated without evidence of increased toxicity of the combination relative to either as a single agent. Importantly, rates of myelosuppression were comparable to single-agent aza in this population. There was evidence of clinical activity with a high CR rate and rapid time to initial response, with evidence of clinical benefit associated with TI in a majority of RARA+ ND unfit AML pts. Use of the novel blood-based biomarker test to predict sensitivity to SY-1425 in AML pts was supported by clinical outcomes, with higher response rates and a more rapid onset in RARA+ vs RARA- pts, whose responses were consistent with single-agent aza. SY-1425 + aza shows potential as a novel targeted regimen for the treatment of RARA+ ND unfit AML and warrants further development in this genomically defined subset of AML pts, as well as other related RARA+ pt populations. Updated data, including mature duration of response and survival, will be presented. Disclosures Cluzeau: Celgene: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Menarini: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees. Vigil:BerGenBio ASA: Research Funding. Rousselot:Pfizer: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy; Novartis: Consultancy; Takeda: Consultancy; Incyte: Consultancy, Research Funding. Rizzieri:Acrobiotech: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Mustang: Membership on an entity's Board of Directors or advisory committees; Celltrion: 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; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Stemline: 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; Kite: Honoraria, Speakers Bureau; Karyopharm: Honoraria, 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; AROG: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Liesveld:Abbvie: Honoraria; Onconova: Other: data safety monitoring board. Fenaux:Abbvie: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Jazz: Honoraria, Research Funding. Braun:Servier: Research Funding; Daiichi Sankyo: Honoraria. Savona:Ryvu: Consultancy; Karyopharm: Consultancy, Current equity holder in publicly-traded company; Gilead: Consultancy; AbbVie: Consultancy; Boehringer Ingelheim: Patents & Royalties; BMS: Consultancy; TG Therapeutics: Consultancy, Research Funding; Sunesis: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Astex: Consultancy, Research Funding. Kelly:Syros Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Volkert:Syros Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Zhou:Syros Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company; Incyte: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Kang-Fortner:Syros Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Roth:Syros Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Stein:Amgen: Consultancy; Agios Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Syndax: Consultancy, Research Funding; Seattle Genetics: Consultancy; Bayer: Research Funding; Syros: Membership on an entity's Board of Directors or advisory committees; PTC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Biotheryx: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.
Published: 2020

38. Comparison of a Combination of Vosaroxin (VOS) and Intermediate-Dose Cytarabine (IDAC) with Idac for the Consolidation Therapy of Younger Patients with Favorable- and Intermediate-Risk Acute Myeloid Leukemia (AML) in First Complete Remission (CR): Preliminary Results of a Randomized Phase 2 R4-VOS Study of the French ALFA-Filo AML Intergroup

Author: Xavier Thomas, Chantal Himberlin, Anne Banos, Clémence Loiseau, Emmanuel Raffoux, Corentin Orvain, Amine Belhabri, Isabelle Luquet, Christian Recher, Mathilde Hunault, Norbert Vey, Pierre Peterlin, Sylvain Chantepie, Christine Terré, Claude Gardin, Ariane C Mineur, Eric Delabesse, Cécile Pautas, Claude Preudhomme, Romain Guieze, Jean Francois Hamel, Emilie Lemasle, Martin Carre, Karine Celli-Lebras, Arnaud Pigneux, Hervé Dombret, Jean-Francois Brasme, and Marc Bernard
Subjects: Oncology, medicine.medical_specialty, business.industry, Immunology, Complete remission, Myeloid leukemia, Cell Biology, Hematology, Biochemistry, Vosaroxin, Consolidation therapy, chemistry.chemical_compound, chemistry, Internal medicine, medicine, Cytarabine, Intermediate risk, business, medicine.drug
Abstract: In spite of CR rates of 75-80% currently achieved with anthracycline-cytarabine regimens in younger patients with favorable and intermediate-risk AML, relapse remains a major issue. The French AML intergroup launched the BIG-1 trial in 2015 in order to test different strategies aiming at reducing relapse rate and improving survival. All patients with previously untreated non-APL and non-CBF AML aged 18-60 years are eligible for trial participation which is still ongoing. The trial design includes several randomizations (R): Idarubicin vs daunorubicin for induction (R1), HDAC vs IDAC for consolidation (R2), post-transplant GVHD prophylaxis modalities (R3). R4 consists of nested randomized phase 2-3 trials testing the addition of new drugs to the IDAC or HDAC backbones during the consolidation phase. The protocol was designed to allow the sequential evaluation of several new agents over the trial period. Vosaroxin (VOS) has shown antileukemic activity (Advani, Clin Cancer Res 2010). The combination of VOS and IDAC showed higher CR rate and a non-significant OS benefit as compared to a placebo-IDAC arm in a large phase 3 trial in patients with refractory/relapsed AML (Ravandi Lancet Oncol 2015). We hypothesized that the addition of VOS to IDAC would improve LFS as compared to IDAC alone when given during the consolidation phase. Methods. Eligibility criteria in the BIG-1 trial include: previously untreated AML according to WHO 2016 classification (AML secondary to an untreated myelodysplastic syndrome allowed), age 18-60, ECOG PS 0-2, no cardiac contra-indication to anthracyclines. Patients with APL and patients with CBF-AML are excluded. Eligibility criteria for R4 randomization were: Patients in first CR/CRp/CRi following 1 or 2 courses of induction chemotherapy according to the BIG-1 protocol; ELN2010 favorable- and intermediate-risk groups; ECOG PS ≤ 3; Absence of severe uncontrolled infection. Patients were scheduled to receive Cytarabine: 1.5 gr/m² twice daily on D1, 3, 5 with or without Vosaroxin: 70 mg/m² on D1 and D4 per cycle for a maximum of three cycles at 4-6 weeks intervals. Patients scheduled for allo-SCT or those who had reached CR after 2 induction cycles were to receive only 2 cycles of VOS-IDAC/IDAC. R4-VOS sub-trial was designed to detect an increase of the 18-month LFS from 55% to 75% using a two-step phase 2-3 study. With type I and II errors set at 20% and using a one-sided test, 70 patients had to be randomized. If the predefined statistical objectives were met, study would resume recruiting 130 additional patients in the phase 3 part for a total of 200 patients. Results. 70 patients (35 in each arm), median age 47, ELN 2010 favorable and intermediate risk groups, have been included. 94% had de novo AML with NPM1 mutations in 46% and FLT3-ITD in 20%. As shown in the Table, patients and disease characteristics were not different between the 2 arms except for slightly more patients in CRi in the VOS-IDAC arm. Patients received a median of 4 chemotherapy cycle (including induction; range 3-4) without difference between the treatment arms. 13 patients (18.5%) received an alloSCT (VOS-IDAC: 5, IDAC: 8). Time between cycle 1 and cycle 2 was significantly longer in the VOS-IDAC arm (p= 0.017). Hematologic toxicity was higher in the VOS-IDAC group with a significantly longer neutropenia duration after each cycle, a greater number of RBC and Platelet transfusions, a significantly greater number of days with antibiotics and antifungal therapies and days with fever (during cycle 1). There were also significantly more cutaneous toxicity, mild nausea/vomiting and diarrhea in the VOS-IDAC arm. With a median follow-up of 19 months, 14 and 15 patients relapse in the VOS-IDAC vs IDAC arms respectively. The study primary endpoint has not been reached and LFS was not significantly higher in the VOS-IDAC arm (18-month LFS of 51% vs 46% for VOS-IDAC vs IDAC respectively; see Figure) even after accounting for allo-SCT as a time-dependent variable (p-value=.49). The 2-year CIR was 51% vs 46% (p=NS) and 2-year OS was 88% vs 68% (p=NS). Conclusion, the study's primary endpoint has not been met and results fail to show a significant improvement of 18-month LFS with the addition of VOS to IDAC consolidation of favorable/intermediate-risk AML in first CR. The phase 3 part of the trial will not open. The BIG-1 trial is still ongoing and uses the same design to tests addition of other drugs to the IDAC/HDAC consolidation backbone. Disclosures Guieze: abbvie: Honoraria, Other: advisory board, travel funds; janssen cilag: Honoraria, Other: advisory board, travel funds; roche: Other: travle funds; gilead: Honoraria, Other: travel funds; astrazanecka: Honoraria, Other: advisory board. Dombret:Pfizer: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Nova: Consultancy, Research Funding; Celgene: Consultancy; Jazz Pharma: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Sunesis: Consultancy; Servier: Consultancy, Research Funding; Daiichi Sankyo: Consultancy; Astellas: Consultancy; Menarini: Consultancy; Janssen: Consultancy; Cellectis: Consultancy; Shire-Baxalta: Consultancy; Immunogen: Consultancy; Otsuka: Consultancy; Abbvie: Consultancy. Hunault:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Diachi: Membership on an entity's Board of Directors or advisory committees; Jansen: Honoraria; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees.
Published: 2020

39. Addition of Brentuximab Vedotin to Gemcitabine in Relapsed or Refractory T-Cell Lymphoma: Results of a Lysa Multicenter, Phase II Study. 'the TOTAL Trial'

Author: Nicolas Daguindau, Hassan Farhat, Vincent Camus, Sabine Tricot, Philippe Gaulard, Catherine Thieblemont, Franck Morschhauser, Thierry Lamy De La Chapelle, Emmanuel Bachy, Laurence de Leval, Kamel Laribi, Marc André, Maya Hacini, Adrien Chauchet, Bernard Drenou, Anne Banos, Richard Delarue, Hacene Zerazhi, Guillaume Cartron, Steven Le Gouill, Marie Maerevoet, Nicole Straetmans, Sylvia Snauwaert, Olivier Tournilhac, Emmanuelle Nicolas-Virelizier, Emmanuel Gyan, Céline Bossard, Caroline Delette, Kamal Bouabdallah, Stéphanie Guidez, David Sibon, Marie Parrens, Gandhi Damaj, Pierre Feugier, Jehan Dupuis, and Loic Ysebaert
Subjects: Oncology, medicine.medical_specialty, business.industry, Refractory T-Cell Lymphoma, Immunology, Phases of clinical research, Cell Biology, Hematology, Biochemistry, Gemcitabine, Internal medicine, medicine, business, Brentuximab vedotin, medicine.drug
Abstract: Background Peripheral T-cell lymphoma (PTCL) is a heterogeneous and accounts for approximately 10% of all lymphomas. Outcome of relapse/refractory (R/R) PTCL is poor with median progression-free survival (PFS) and overall survival (OS) of 3 and 6 months in the absence of stem-cell transplantation (SCT). [Mak, JCO, 2013]. Brentuximab vedotin (BV) monotherapy is approved for R/R systemic anaplastic large cell-lymphoma (ALCL) based on 86% overall response rate (ORR) and 57% complete remission (CR). [Pro, JCO, 2012]. In other CD30-positive (CD30+) R/R PTCL, the ORR of BV is 41%. Gemcitabine (G) used as monotherapy in control arm in the randomized phase 3 LUMIERE trial, provided ORR and CR rates of 35 and 22% respectively. [O'Connor, JCO, 2019]. Considering these results we designed a phase 2 study for R/R CD30+ PTCL combining G and BV with the primary end point to increase the ORR by 15%, compared to G monotherapy. Patients (pts) and Methods: Pts with histologically confirmed CD30+ (≥5%) PTCL who failed or were refractory to 1-3 prior lines of systemic therapy, with measurable disease and ECOG performance status < 3 were eligible. Pts received an induction of 4 cycles of G-BV (28-days cycles; G: 1000 mg/m² at D1 and D15 plus BV: 1.8 mg/kg at D8). Pts with CR or partial remission (PR) and non-eligible for SCT, received BV maintenance 1.8 mg/kg at D1 (21-days cycles) up to 12 cycles. The primary endpoint was the ORR (CR + PR) according to Lugano criteria based on CT-scan. Secondary objectives included tolerance and safety, DOR, PFS, OS and impact of BV maintenance. Eligible pts were censored at time of SCT. (NCT03496779). Results: From April 2018 to October 2019, 71 pts were included. Pathology central review according to WHO 2017 criteria, so far available for 50 patients, confirmed angioimmunoblastic T-cell lymphoma (AITL) (22 ; 31%); nodal PTCL-TFH (5 ; 7%); PTCL-NOS (5 ; 7%); ALK- ALCL (10 ; 14.1%) ; ALK+ ALCL (4 ; 5.6%), Enteropathy associated T-cell lymphoma (EATL) (2 ; 2.8%); unclassified PTCL (2 ; 2.8%). There were 47 male and 24 female with a median age of 66 years (20-79) and 17 pts were > 75 years. Median time from diagnosis to enrolment was 9.4 months (range, 6-21). Sixty-five pts (91.6%) presented with stage III-IV. The number of prior lines of therapy were 1 (57 pts), 2 (11 pts) or 3 (3 pts), all pts had received previous CHOP-like chemotherapy, 11 pts previous autologous SCT, 5 pts epigenetic modifiers and 39.4% were refractory to their last line of treatment prior to inclusion. The cut-off date of this analysis was 01/31/2020. The 4 cycles of G-BV induction were completed in 45 pts (63%). The reasons for early discontinuation were progression (21 pts), death (3 pts) or adverse event (2 pts). In intention-to-treat analysis, the ORR at the end of induction (EOI) was 47.9% including CR (14 pts; 19.7%), PR (20 pts; 28.2%). PET performed in all patients reaching EOI showed overall and complete metabolic responses in 45.1 and 23.9%, respectively. During G-BV induction 58 pts (81.7%) had at least one G > 3 adverse event (AE) including neutropenia (67.2%), thrombopenia (17.2%), infections (15.5%), peripheral neuropathy (PN) (5.2%) and cardiac event (5.2%). Overall PN of any grade was recorded in 8/71 patients (11%) during G-BV induction and caused BV withdrawal in one case. Among the 34 responding pts after EOI, 27 pts began BV maintenance and 7 pts remain on maintenance at cut-off date. Eight pts were removed from the study due to SCT eligibility, either after the 4 GBV induction (4 pts) or after 1 or 2 maintenance BV cycles (4 pts). With a median follow-up (FU) of 9.5 (0.5-19.4) months, median PFS is 4.5 months (95%CI [3.5 - 10]) and median OS is 12 months (95%CI [8.6 - NR]). Among the 34 patients in PR/CR after induction, the duration of response (DOR) is 12.8 months (95%CI [10.3 - NR]). At last FU were recorded 32 deaths. Disease status at time of death was PD (25 pts), CR (1 pt) NE or missing (6 pts). Conclusion: The addition of BV to G increases the overall response rate by 15% in the treatment of R/R CD30+ PTCL. OS data are encouraging for this overall R/R patient population but PFS is overall short and a longer FU is mandatory. Especially the DOR of pts achieving CR or PR after 4 cycles of G-BV exceeds 1 year on BV maintenance. This combination is generally well tolerated and this study suggests that G-BV combination could be an interesting alternative for R/R CD30+ PTCL. Disclosures Tournilhac: Janssen: Consultancy, Honoraria, Other: Travel grant; INNATE Pharma: Consultancy, Honoraria; GILEAD: Consultancy, Honoraria, Other: Travel Grant; ABBVIE: Consultancy, Honoraria, Other: Travle grant; Takeda: Consultancy, Honoraria, Other: Travel grant. Laribi:novartis: Honoraria, Research Funding; amgen: Research Funding; abbvie: Honoraria, Research Funding; takeda: Research Funding. Ysebaert:AbbVie: Consultancy; Roche: Consultancy; Janssen: Consultancy. Guidez:BMS: Honoraria; TAKEDA: Honoraria; Service Hématologie et Thérapie cellulaire CHU POITIERS: Current Employment; AMGEN: Honoraria; CELGENE: Honoraria; JANSEN: Honoraria. Le Gouill:Loxo Oncology at Lilly: Consultancy; Roche Genentech, Janssen-Cilag and Abbvie, Celgene, Jazz pharmaceutical, Gilead-kite, Loxo, Daiichi-Sankyo and Servier: Honoraria. André:Celgene: Other, Research Funding; Takeda: Consultancy; Bristol-Myers-Squibb: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Karyopharm: Consultancy; Gilead: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Novartis: Consultancy, Research Funding; Amgen: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Johnson & Johnson: Research Funding; CHU UCL Namur, site Godinne, Yvoir, Belgium: Current Employment; Roche: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Abbvie: Consultancy; Seattle Genetics: Consultancy. Dupuis:Henri Mondor University Hospital Creteil France: Current Employment. Thieblemont:Roche, Amgen, Kyte Gilead, Celgene, Abbvie, Novartis, Cellectis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Roche, Hospita: Research Funding; Cellectis: Speakers Bureau. Bachy:Beigene: Membership on an entity's Board of Directors or advisory committees; Roche, Gilead: Consultancy; Amgen: Research Funding; Roche, Celgene, Amgen, Janssen, Gilead, Novartis, Sanofi: Honoraria. Morschhauser:Celgene: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; F. Hoffmann-La Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Epizyme: Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy; Servier: Consultancy; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Feugier:janssen: Consultancy, Honoraria, Research Funding; gilead: Consultancy, Honoraria, Research Funding; roche: Consultancy, Honoraria, Research Funding; astrazeneca: Consultancy, Honoraria, Research Funding; abbvie: Consultancy, Honoraria, Research Funding. Cartron:F. Hoffmann-La Roche: Consultancy, Honoraria; Abbvie: Honoraria; Jansen: Honoraria; Celgene: Consultancy, Honoraria; Sanofi: Honoraria; Gilead: Honoraria. Camus:ROCHE: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); JANSSEN: Honoraria; AMGEN: Honoraria; PFIZER: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Sibon:takeda france: Consultancy. Snauwaert:roche: Other: travel; janssen: Other: travel; abbvie: Other. Delarue:BMS: Other: stock options ; Celgene/BMS: Current Employment. De Leval:Abbvie: Honoraria; Lausanne University Hospital & Lausanne University Institute of Pathology: Current Employment; Roche Diagnostics: Honoraria; Lunaphore Technologies SA: Consultancy, Honoraria. Gaulard:CHU Henri Mondor, Assistance Publique-Hôpitaux de Paris: Current Employment; TAKEDA: Consultancy, Honoraria, Research Funding; INNATE PHARMA: Research Funding; Roche: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company).
Published: 2020

40. Obinutuzumab and ibrutinib induction therapy followed by a minimal residual disease-driven strategy in patients with chronic lymphocytic leukaemia (ICLL07 FILO): a single-arm, multicentre, phase 2 trial

Author: Carmen Aanei, Florence Nguyen-Khac, Luc Mathieu Fornecker, Marie-Sarah Dilhuydy, Anne Banos, Olivier Tournilhac, Stéphane Leprêtre, Anne-Sophie Michallet, Loic Ysebaert, Thérèse Aurran, Christelle Portois, Jean Pierre Vilque, Cécile Tomowiak, Veronique Leblond, Caroline Dartigeas, Pierre Feugier, Guillaume Cartron, Philippe Carassou, Rémi Letestu, Bruno Villemagne, Gilles Salles, Florence Cymbalista, Fabien Subtil, Vincent Levy, Kamel Laribi, Beatrice Mahe, Malgorzata Truchan Graczyk, Alain Delmer, Frederique Orsini, Brigitte Pegourie, Magali Le Garff-Tavernier, Michel Ticchioni, Sophie de Guibert, Valérie Rouille, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
Subjects: Male, medicine.medical_specialty, Neoplasm, Residual, Cyclophosphamide, Gastrointestinal Diseases, Population, Antibodies, Monoclonal, Humanized, Drug Administration Schedule, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Piperidines, Obinutuzumab, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, education, ComputingMilieux_MISCELLANEOUS, Aged, education.field_of_study, Intention-to-treat analysis, Performance status, business.industry, Adenine, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, Minimal residual disease, Leukemia, Lymphocytic, Chronic, B-Cell, Thrombocytopenia, 3. Good health, Fludarabine, Survival Rate, Pyrimidines, Treatment Outcome, chemistry, 030220 oncology & carcinogenesis, Ibrutinib, Mutation, Pyrazoles, Female, Tumor Suppressor Protein p53, business, Immunoglobulin Heavy Chains, 030215 immunology, medicine.drug
Abstract: In patients with chronic lymphocytic leukaemia, achievement of a complete response with minimal residual disease of less than 0·01% (ie,1 chronic lymphocytic leukaemia cell per 10 000 leukocytes) in bone marrow has been associated with improved progression-free survival. We aimed to explore the activity of induction therapy for 9 months with obinutuzumab and ibrutinib, followed up with a minimal residual disease-driven therapeutic strategy for 6 additional months, in previously untreated patients.We did a single-arm, phase 2 trial in 27 university hospitals, general hospitals, and specialist cancer centres in France. Eligible patients were at least 18 years old and previously untreated, and had immunophenotypically confirmed B-cell chronic lymphocytic leukaemia; an Eastern Cooperative Oncology Group (ECOG) performance status score of less than 2; a Binet stage C according to IWCLL 2008 criteria or Binet stage A and B with active disease; no 17p deletion or absence of p53 mutation; and were considered medically fit. In the first part of the study (induction phase), all participants received eight intravenous infusions of obinutuzumab 1000 mg over six 4-weekly cycles and oral ibrutinib 420 mg once per day for 9 months. In part 2, after assessment on day 1 of month 9, patients with a complete response and bone marrow minimal residual disease of less than 0·01% received only oral ibrutinib 420 mg once per day for 6 additional months. Patients with a partial response, or with a complete response and bone marrow minimal residual disease of 0·01% or more, received 6 months of four 4-weekly cycles of intravenous fludarabine, cyclophosphamide, and obinutuzumab 1000 mg, alongside continuing ibrutinib 420 mg once per day. The primary endpoint was the proportion of patients achieving a complete response with bone marrow minimal residual disease less than 0·01% on day 1 of month 16 assessed by intention to treat (ITT). This trial is registered with ClinicalTrials.gov (number NCT02666898) and is still open for follow-up.Between Oct 27, 2015, and May 16, 2017, 135 patients were enrolled. After induction treatment (day 1 of month 9), 130 patients were evaluable, of which ten (8%) achieved a complete response with bone marrow minimal residual disease of less than 0·01% and were assigned to ibrutinib, and 120 (92%) were assigned to ibrutinib plus fludarabine, cyclophosphamide, and obinutuzumab. After minimal residual disease-guided treatment (day 1 of month 16), 84 (62%, 90% CI 55-69) of 135 patients (ITT population) achieved a complete response with bone marrow minimal residual disease of less than 0·01%. The most common haematological adverse event was thrombocytopenia (in 45 [34%] of 133 patients at grade 1-2 in months 1-9 and in 43 [33%] of 130 patients at grade 1-2 in months 9-15). The most common non-haematological adverse events were infusion-related reactions (in 83 [62%] patients at grade 1-2 in months 1-9) and gastrointestinal disorders (in 62 [48%] patients at grades 1 and 2 in months 9-15). 49 serious adverse events occurred, most frequently infections (ten), cardiac events (eight), and haematological events (eight). No treatment-related deaths occurred.Obinutuzumab and ibrutinib induction therapy followed by a minimal residual disease driven strategy is safe and active in patients with previously untreated chronic lymphocytic leukaemia. With longer follow-up, including assessing the evolution of minimal residual disease, if response is maintained, this strategy could be an option in the first-line setting in patients with chronic lymphocytic leukaemia, although randomised evidence is needed.Roche, Janssen.
Published: 2019

41. A phase 2 study of rituximab, bendamustine, bortezomib and dexamethasone for first-line treatment of older patients with mantle cell lymphoma

Author: Loic Ysebaert, Anne Banos, Vincent Delwail, Roch Houot, Nicolas Daguindau, Reda Garidi, Margaret Macro, Ghandi Damaj, Bertrand Joly, Jean Pierre Vilque, Sylvain Carras, Mary Callanan, Fabrice Jardin, Marie Pierre Moles, Magda Alexis, Steven Le Gouill, Emmanuelle Tchernonog, Laurent Voillat, Hacene Zerazhi, Christiane Mounier, J. Fleury, Sandy Amorin, Anne Moreau, Jean Michel Pignon, Adrian Tempescul, Véronique Dorvaux, Yazid Arkam, Luc Fornecker, Caroline Dartigeas, Cecile Chabrot, Philippe Solal Celigny, Pierre Feugier, Remy Gressin, Anna Schmitt, Jean Fontan, Clémentine Sarkozy, Nadine Morineau, Jehan Dupuis, Selim Corm, Krimo Bouadallah, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Service d'Hématologie [CH Annecy], CH Annecy, CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Département de Pathologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Dpt hématologie [CHU Bordeaux], CHU Bordeaux [Bordeaux], Département d'Hématologie Clinique [CHU Rennes], CHU Pontchaillou [Rennes], Département d’Hématologie Clinique [CHU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Service d'hématologie (CH de Dunkerque), Centre Hospitalier Dunkerque, Service Hématologie [CH Métropole Savoie, Chambery], Centre Hospitalier Métropole Savoie [Chambéry], Hôpital de Bayonne, CH de la Côte Basque, Hématologie de liaison avec Institut de Cancérologie de la Loire [CHU de Saint-Etienne], CHU Saint-Etienne, Centre hospitalier universitaire Henri-Mondor [Créteil], Hôpital Universitaire de Caen, Laboratoire d'Hématologie Biologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d’Hématologie [CHU de Clermont Ferrand], Centre Hospitalier Universitaire de Clermont-Ferrand, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Département d’Hématologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service hématologie Amiens, CHU Amiens-Picardie, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Service d'hématologie [CHR Metz-Thionville], Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Service d'Hématologie [Bordeaux], Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex-Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Diderot - Paris 7 (UPD7), Hôpital Saint-Quentin, Service d'hématologie et oncologie [Centre Hospitalier de Chalon-sur-Saône William Morey], Centre Hospitalier Chalon-sur-Saône William Morey, Hôpital de Corbeil, Service d'Oncologie médicale [Clinique Victor Hugo], Clinique Victor Hugo, Centre Catherine-de-Sienne [Nantes] (CCS), Département d'Hématologie Clinique [CHU d'Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Médecine Interne Onco-hématologie, Centre Hospitalier Général, Hopital d'Avignon, Service d'hématologie, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Service Hématologie, Mulhouse, Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Hématologie Biologique [CHR d'Orléans], Centre Hospitalier Régional d'Orléans (CHR), Service d’Oncologie Hématologique et Thérapie Cellulaire [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie [Nantes], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’Hématologie Clinique [Rennes], Service d’Hématologie Biologique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Laboratoire d'Hématologie [CHU Amiens], Centre Hospitalier Henri Duffaut (Avignon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Régional d'Orléans (CHRO), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Bendamustine, Male, medicine.medical_specialty, Time Factors, Non-Hodgkin Lymphoma, Lymphoma, Mantle-Cell, Neutropenia, Gastroenterology, Dexamethasone, Disease-Free Survival, Article, Bortezomib, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Bendamustine Hydrochloride, Humans, Survival rate, Aged, Aged, 80 and over, business.industry, Hematology, Middle Aged, medicine.disease, Minimal residual disease, 3. Good health, Lymphoma, Survival Rate, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Rituximab, Mantle cell lymphoma, Female, business, 030215 immunology, medicine.drug
Abstract: International audience; We present results of a prospective, multicenter, phase II study evaluating rituximab, bendamustine, bortezomib and dexamethasone as first-line treatment for patients with mantle cell lymphoma aged 65 years or older. A total of 74 patients were enrolled (median age, 73 years). Patients received a maximum of six cycles of treatment at 28-day intervals. The primary objective was to achieve an 18-month progression-free survival rate of 65% or higher. Secondary objectives were to evaluate toxicity and the prognostic impact of mantle cell lymphoma prognostic index, Ki67 expression, [18F]fluorodeoxyglucose-positron emission tomography and molecular minimal residual disease, in peripheral blood or bone marrow. With a median follow-up of 52 months, the 24-month progression-free survival rate was 70%, hence the primary objective was reached. After six cycles of treatment, 91% (54/59) of responding patients were analyzed for peripheral blood residual disease and 87% of these (47/54) were negative. Four-year overall survival rates of the patients who did not have or had detectable molecular residual disease in the blood at completion of treatment were 86.6% and 28.6%, respectively (P
Published: 2018

42. Improved Survival by Adding Lomustine to Conventional Chemotherapy for Elderly Patients With AML Without Unfavorable Cytogenetics: Results of the LAM-SA 2007 FILO Trial

Author: Julien Asselineau, Anne Banos, Caroline Bonmati, Romain Guieze, Mario Ojeda-Uribe, Eric Jourdan, Ariane C Mineur, Norbert Ifrah, Arnaud Pigneux, Hacene Zerazhi, Marie C. Béné, Louis-Rachid Salmi, Norbert Vey, Pascale Cornillet-Lefebvre, Marc Bernard, Christian Recher, Eric Delabesse, Jean-Christophe Ianotto, Jean-Yves Cahn, Isabelle Luquet, Roselyne Delepine, Jacques Delaunay, Pierre-Yves Dumas, Yosr Hishri, Luc Fornecker, Mathilde Hunault, Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie Clinique et Thérapie Cellulaire [CHU Bordeaux], Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux], Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Service d'Hématologie Clinique [Nantes] (Unité d'Investigation Clinique), Centre hospitalier universitaire de Nantes (CHU Nantes), Société d'Hématologie du Confluent [Nantes], Société D'hematologie Du Confluent - Nantes, Service d’Hématologie Adulte [Hôpitaux de Brabois, CHU Nancy], Centre Hospitalier Universitaire de Nancy (CHU Nancy), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Laboratoire d'hématologie, Centre Hospitalier Universitaire de Reims (CHU Reims), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital de Bayonne, Centre Hospitalier de la Côte Basque (CHCB), Laboratoire de Spectrométrie de Masse BioOrganique [Strasbourg] (LSMBO), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Département d'Hématologie [CHU Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Médecine Interne Onco-hématologie, Centre Hospitalier Général, Centre Hospitalier Henri Duffaut (Avignon), Unité de Soutien Méthodologique à la Recherche Clinique (USMR), Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), CH de la Côte Basque, Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Institut Universitaire du Cancer Toulouse - Oncopôle (IUCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), and Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 03 medical and health sciences, Myelogenous, 0302 clinical medicine, Internal medicine, medicine, Idarubicin, Cumulative incidence, Chemotherapy, business.industry, Lomustine, medicine.disease, 3. Good health, Regimen, Leukemia, 030104 developmental biology, 030220 oncology & carcinogenesis, Cytarabine, business, medicine.drug
Abstract: Purpose Acute myeloid leukemia (AML) in elderly patients has a poor prognosis. In an attempt to improve outcome for these patients, the prospective open-label phase III LAM-SA 2007 (Adding Lomustine to Chemotherapy in Older Patients With Acute Myelogenous Leukemia (AML), and Allogeneic Transplantation for Patients From 60 to 65 Years Old) trial randomly assigned patients to a standard induction regimen with lomustine added or to a consolidation regimen with cytarabine and idarubicin. Patients and Methods Adults age 60 years or older with previously untreated AML who were fit to receive intensive chemotherapy and who were without unfavorable cytogenetics received standard chemotherapy with lomustine (idarubicin, cytarabine, and lomustine [ICL]) or without (idarubicin and cytarabine [IC]). The primary objective of the study was overall survival (OS); secondary objectives were response rate, cumulative incidence of relapse (CIR), event-free survival (EFS), and safety. Results From February 2008 to December 2011, 459 patients were enrolled. Comparing patients in the IC and ICL arms, complete response or complete response with incomplete recovery was achieved in 74.9% versus 84.7% ( P = .01). The proportional hazards assumption was rejected for OS ( P = .02), which led us to consider two separate time intervals: during and after induction. There was no significant difference between the two arms during induction, although induction deaths were 3.7% versus 7.7%, respectively ( P = .11). However, significantly better results were observed after induction with an improved 2-year OS of 56% in the ICL arm versus 48% in the IC arm ( P = .02). At 2 years, EFS was improved at 41% in the ICL arm versus 26% in the IC arm ( P = .01). The CIR at 2 years was 41.2% in the ICL arm versus 60.9% in the IC arm ( P = .003). Grade 3 and 4 toxicities, mostly hematologic, were significantly higher in the ICL arm ( P = .04), and fewer patients required a second treatment after ICL. Conclusion Adding lomustine to standard chemotherapy significantly improved the outcome of elderly patients with AML.
Published: 2018

43. Increased rituximab exposure does not improve response and outcome of patients with chronic lymphocytic leukemia after fludarabine, cyclophosphamide, rituximab. A French Innovative Leukemia Organization (FILO) study

Author: Frédérique Orsini-Piocelle, Alain Delmer, Olivier Tournilhac, Stéphane Leprêtre, Rémi Letestu, Mira Tout, Thérèse Aurran, David Ternant, Sophie de Guibert, Phan Letuan, Emmanuelle Ferrant, Valérie Rouille, Guillaume Cartron, Bruno Villemagne, Pierre Feugier, Boris Guiu, Caroline Dartigeas, Anne Banos, Beatrice Mahe, Jehan Dupuis, Anne-Laure Gagez, Veronique Leblond, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
Subjects: Oncology, medicine.medical_specialty, business.industry, Chronic lymphocytic leukemia, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, 030204 cardiovascular system & hematology, medicine.disease, 3. Good health, Cyclophosphamide/Rituximab, Fludarabine, 03 medical and health sciences, Leukemia, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, Rituximab, Online Only Articles, business, ComputingMilieux_MISCELLANEOUS, medicine.drug
Abstract: International audience
Published: 2018

44. R-CHOP 14 with or without radiotherapy in non-bulky limited-stage diffuse large B-cell lymphoma (DLBCL)

Author: Gandhi Damaj, Katell Le Du, J. Fleury, Jean Pierre Marolleau, Vincent Delwail, Krimo Bouabdallah, Anne Devillers, Guillaume Cartron, Pierre Soubeyran, Valérie Costes, Olivier Tournilhac, Pascal Godmer, Emmanuel Gyan, Marie C. Béné, Steven Le Gouill, Marie-Pierre Moles, Jean Philippe Vuillez, Mohamed Benchalal, Philippe Colombat, Jérôme Cornillon, Thierry Fest, Hervé Maisonneuve, Eric Deconinck, Kamel Laribi, Vanessa Szablewski, Roch Houot, Bernard Branger, Thierry Lamy, Remy Gressin, Anne Banos, CHU Pontchaillou [Rennes], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de référence des mastocytoses (CEREMAST), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Plateforme de génétique moléculaire des cancers d'Aquitaine, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Service d'hématologie, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], CHU Grenoble-Hôpital Michallon, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Hôpital de Bayonne, Centre Hospitalier de la Côte Basque (CHCB), Centre Eugène Marquis (CRLCC), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de médecine interne [CHU Bretagnes Atlantique], CHU Bretagnes Atlantique, Centre hospitalier La Roche-Sur-Yon, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d'hématologie clinique, Université de Rennes (UR)-Hôpital Pontchaillou, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Réseau Sécurité Naissance - Naître Ensemble, Nantes, Département de médecine nucléaire [Rennes], CRLCC Eugène Marquis (CRLCC), Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by Roche., Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), CHU Saint-Etienne, CH de la Côte Basque, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), BOUAKAZ, Amel, Centre de référence des mastocytoses, Institut Bergonié - CRLCC Bordeaux, Regulation of Bcl2 and p53 networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA - Département NOHMAD - Equipe 10), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias - Clermont Auvergne (CHELTER), Université Clermont Auvergne (UCA), and Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Male, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, genetic structures, Clinical Trials and Observations, [SDV]Life Sciences [q-bio], Kaplan-Meier Estimate, Biochemistry, Gastroenterology, law.invention, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, International Prognostic Index, Randomized controlled trial, law, immune system diseases, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Prospective Studies, Child, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Hazard ratio, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, Chemotherapy regimen, Progression-Free Survival, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Vincristine, 030220 oncology & carcinogenesis, Female, Lymphoma, Large B-Cell, Diffuse, Rituximab, medicine.drug, Adult, medicine.medical_specialty, Randomization, Immunology, 03 medical and health sciences, Internal medicine, medicine, Humans, Progression-free survival, Cyclophosphamide, business.industry, Patient Selection, Cell Biology, medicine.disease, Surgery, Doxorubicin, Prednisone, business, Diffuse large B-cell lymphoma, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: International audience; The benefit of radiotherapy (RT) after chemotherapy in limited-stage diffuse large B-cell lymphoma (DLBCL) remains controversial. We conducted a randomized trial in patients with nonbulky limited-stage DLBCL to evaluate the benefit of RT after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Patients were stratified according to the modified International Prognostic Index, including lactate dehydrogenase, Eastern Cooperative Oncology Group performance status, age, and disease stage. The patients received 4 or 6 consecutive cycles of R-CHOP delivered once every 2 weeks, followed or not by RT at 40 Gy delivered 4 weeks after the last R-CHOP cycle. All patients were evaluated by fluorodeoxyglucose-positron emission tomography scans performed at baseline, after 4 cycles of R-CHOP, and at the end of treatment. The primary objective of the trial was event-free survival (EFS) from randomization. The trial randomly assigned 165 patients in the R-CHOP arm and 169 in the R-CHOP plus RT arm. In an intent-to-treat analysis with a median follow-up of 64 months, 5-year EFS was not statistically significantly different between the 2 arms, with 89% ± 2.9% in the R-CHOP arm vs 92% ± 2.4% in the R-CHOP plus RT arm (hazard ratio, 0.61; 95% confidence interval [CI], 0.3-1.2; = .18). Overall survival was also not different at 92% (95% CI, 89.5%-94.5%) for patients assigned to R-CHOP alone and 96% (95% CI, 94.3%-97.7%) for those assigned to R-CHOP plus RT ( = not significant). R-CHOP alone is not inferior to R-CHOP followed by RT in patients with nonbulky limited-stage DLBCL. This trial was registered at www.clinicaltrials.gov as #NCT00841945.
Published: 2018

45. OUTCOME OF PATIENTS WITH C-MYC REARRANGED DIFFUSE LARGE B CELL LYMPHOMA ASSOCIATED OR NOT WITH BCL2 AND/OR BCL6 REARRANGEMENT: A MULTICENTRIC AND RETROSPECTIVE STUDY

Author: Anne Banos, F. Lifermann, Kamal Bouabdallah, A. Saint-Lézer, N. Milpied, S. Favre, Olivier Fitoussi, G. Labouré, C. Dagada, B. Deau-Fisher, C. Botella-Garcia, P. Rispal, and F. Bijou
Subjects: Oncology, Cancer Research, medicine.medical_specialty, business.industry, Retrospective cohort study, Hematology, General Medicine, medicine.disease, BCL6, Internal medicine, medicine, business, Diffuse large B-cell lymphoma
Published: 2019

46. Lenalidomide is safe and active in Waldenström macroglobulinemia

Author: Claire Bories, Sylvain Choquet, Xavier Leleu, Bertrand Arnulf, Pierre Morel, Hélène Demarquette, Stéphanie Poulain, Anne Banos, Olivier Tournilhac, Marie-Odile Petillon, Malek Dib, Charles Herbaux, Beatrice Thielemans, Jana Bakala, Steven Legouill, Audrey Martin, Stéphanie Guidez, Bella Ohyba, Pauline Brice, Véronique Leblond, Lionel Karlin, Gilles Salles, Morgane Nudel, Chanaz Louni, and Guillemette Fouquet
Subjects: medicine.medical_specialty, business.industry, Anemia, Waldenstrom macroglobulinemia, Macroglobulinemia, Hematology, Neutropenia, medicine.disease, Gastroenterology, Surgery, Thalidomide, hemic and lymphatic diseases, Internal medicine, medicine, Rituximab, business, Multiple myeloma, medicine.drug, Lenalidomide
Abstract: Lenalidomide is manageable and effective in multiple myeloma, particularly in elderly patients. Surprisingly, the combination of lenalidomide with rituximab produced clinically significant anemia at 25 mg/day for 21/28 days, the highest possible dose, in Waldenstrom's Macroglobulinemia (WM). We aimed to determine the maximum tolerated dose (MTD) of single agent lenalidomide and determine its impact on WM. RV-WM-0426 is a multicenter dose escalation open label phase 1/2 study of lenalidomide in relapsed/refractory WM (RRWM). Lenalidomide was given orally 21/28 days per cycle for 1 year, at escalated dose of 15 to 20 mg during phase 1 to determine the MTD; the phase 2 part was conducted at the MTD. Seventeen RRWM patients were included. The MTD was established at 15 mg/day 21/28. By ITT analysis, the overall response rate was 29%. With a median follow-up of 36 months, median TTP was 16 months (95% CI 5.5-26), the 5-year OS was 91%. The most frequent adverse events ≥ grade 3 at 15 mg were 14% anemia and 43% neutropenia. The MTD of lenalidomide is 15 mg/day 21/28 days in RRWM. Lenalidomide is active in the treatment of RRWM and the safety profile appears manageable. Future studies may look into combinations of lenalidomide and continuous dosing.
Published: 2015

47. Maintenance therapy with alternating azacitidine and lenalidomide in elderly fit patients with poor prognosis acute myeloid leukemia: a phase II multicentre FILO trial

Author: Didier Bouscary, E. Tavernier, Mathilde Hunault-Berger, A Saad, Chantal Himberlin, Severine Lissandre, Christian Recher, Isabelle Luquet, F Orsini-Piocelle, M-A Couturier, Etienne Daguindau, N. Maillard, M C Béné, Caroline Bonmati, Francois Dreyfus, Martin Carre, J-P Marolleau, A Schmidt-Tanguy, Jacques Delaunay, Norbert Ifrah, Luc Fornecker, Mario Ojeda-Uribe, M Puyade, B. Choufi, J-F Hamel, Arnaud Pigneux, Marc Bernard, Anne Banos, L Sutton, V Rouillé, Laurence Sanhes, Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'hématologie pédiatrique - CHU Reims, Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie [CH Boulogne/Mer], CH Boulogne sur Mer, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut de cancérologie et d'hématologie [Brest], Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire d'Hématologie [CHU Amiens], CHU Amiens-Picardie, Service d'Hématologie [CH Annecy], CH Annecy, Service d'Hématologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie [ CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Service d'Hématologie et thérapie cellulaire [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service d'Hématologie [CH Mulhouse], Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Service d'Hématologie [CH Perpignan], CH Perpignan, Service d'Hématologie [CH Argenteuil], CH Argenteuil, Service d'hématologie (CH de la Côte Basque), Centre Hospitalier de la Côte Basque (CHCB), Département d'Oncologie Médicale et d'Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Service d'hématologie clinique, Université de Rennes (UR)-Hôpital Pontchaillou, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hématologie [CH Béziers], CH Béziers, Service d'Hématologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d'Hématologie Biologique [CHU Nantes], Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’hématologie Clinique [CHU Bordeaux], CHU Bordeaux [Bordeaux], Celgene for providing azacitidine, lenalidomide and financial support for the monitoring., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie [Saint-Etienne], Institut de Cancérologie de la Loire [Saint-Etienne], Le CHCB, Centre Hospitalier de la Côte Basque, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Hématologie Biologique [CHU Toulouse], CHU Toulouse [Toulouse]-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Bernardo, Elizabeth, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3)
Subjects: Oncology, Male, medicine.medical_specialty, Azacitidine, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, Maintenance Chemotherapy, 03 medical and health sciences, 0302 clinical medicine, Maintenance therapy, [SDV.CAN] Life Sciences [q-bio]/Cancer, hemic and lymphatic diseases, Internal medicine, Medicine, Humans, Lenalidomide, Letter to the Editor, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Hematology, business.industry, Myeloid leukemia, Middle Aged, medicine.disease, 3. Good health, Lymphoma, Thalidomide, Survival Rate, Leukemia, Haematopoiesis, Leukemia, Myeloid, Acute, 030220 oncology & carcinogenesis, Immunology, Female, business, 030215 immunology, medicine.drug
Abstract: Maintenance therapy with alternating azacitidine and lenalidomide in elderly fit patients with poor prognosis acute myeloid leukemia: a phase II multicentre FILO trial
Published: 2017

48. A phase II Bayesian sequential clinical trial in advanced Waldenström macroglobulinemia patients treated with bortezomib: interest of addition of dexamethasone

Author: Julie Lejeune, Carole Soussain, Xavier Leleu, Brigitte Dreyfus, Caroline Dartigeas, Véronique Leblond, Stéphane Leprête, Sylvie Chevret, Marie-Sarah Dilhuidy, Anne Banos, Thérèse Aurran, Brigitte Pegourie, Olivier Tournilhac, Herve Oya, Beatrice Mahe, Bruno Anglaret, Caroline Besson, Anne Vekhoff, Pierre Morel, Maya Ouzegdouh, Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie Clinique, CHU La Milétrie, Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Hématologie Clinique, CHU Hotel Dieu, Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Hôpital de Bayonne, CH de la Côte Basque, Unité de Recherche Clinique [CHU Pitié-Salpêtrière], Biologie des Interactions Neurones / Glie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Psychiatry Department and Clinics for Adolescent Medicine, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Service d'Hématologie Clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Laboratoire de Cosmologie, Astrophysique Stellaire & Solaire, de Planétologie et de Mécanique des Fluides ( CASSIOPEE ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Observatoire de la Côte d'Azur, Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), CHU de Poitiers, Centre interdisciplinaire de recherche en biologie ( CIRB ), Collège de France ( CdF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Nutrition, croissance et cancer ( N2C ), Université de Tours-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Centre d'Immunologie de Marseille - Luminy ( CIML ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), CHU Saint-Antoine [APHP], Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias - Clermont Auvergne ( CHELTER ), Université Clermont Auvergne ( UCA ), CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 ( UPD5 ), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier de la Côte Basque (CHCB), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Collège de France (CdF)-PSL Research University (PSL), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias - Clermont Auvergne (CHELTER), Université Clermont Auvergne (UCA), CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Oncology, Male, Cancer Research, medicine.medical_specialty, Kaplan-Meier Estimate, Dexamethasone, Bortezomib, 03 medical and health sciences, 0302 clinical medicine, Overall response rate, immune system diseases, hemic and lymphatic diseases, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, In patient, cardiovascular diseases, Prospective Studies, neoplasms, ComputingMilieux_MISCELLANEOUS, Aged, Bortezomib/rituximab, business.industry, Remission Induction, Waldenstrom macroglobulinemia, Bayes Theorem, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, medicine.disease, Hematologic Diseases, 3. Good health, Surgery, Clinical trial, 030220 oncology & carcinogenesis, Female, Waldenstrom Macroglobulinemia, business, 030215 immunology, medicine.drug
Abstract: In patients with advanced Waldenström macroglobulinemia (WM), overall response rate (ORR) and median progression-free survival (PFS) achieved with bortezomib alone and bortezomib rituximab combination were 27-85% and 7.9 months, and 81% and 16.4 months, respectively. We checked the role of dexamethasone in combination with bortezomib by enrolling in a phase II trial 34 patients with relapsed/refractory WM. Bortezomib (1.3 mg/m
Published: 2017

49. miR-125b and miR-532-3p predict the efficiency of rituximab-mediated lymphodepletion in chronic lymphocytic leukemia patients. A French Innovative Leukemia Organization study

Author: Rémi Letestu, Florence Apparailly, Véronique Leblond, Guillaume Cartron, Olfa Khalifa, Jehan Dupuis, Christian Jorgensen, Sophie de Guibert, Edouard Tuaillon, Isabelle Duroux-Richard, Anne-Laure Gagez, Frédérique Orsini-Piocelle, Anne Banos, Valérie Gouilleux-Gruart, Olivier Tournilhac, Stéphane Leprêtre, Dynamique des interactions membranaires normales et pathologiques (DIMNP), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Service d'hématologie clinique, Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Adaptateurs de signalisation en hématologie (ASIH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13), Service d'hématologie biologique [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017] (GICC UMR 7292 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Hôpital de Bayonne, CH de la Côte Basque, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Hôpital Henri Mondor, Hôpital Lapeyronie, Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier de la Côte Basque (CHCB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), BOUAKAZ, Amel, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université de Tours-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, Lymphocytosis, Lymphocyte, Chronic lymphocytic leukemia, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Cluster Analysis, CD20, biology, Gene Expression Regulation, Leukemic, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Articles, Middle Aged, Prognosis, 3. Good health, Reverse transcription polymerase chain reaction, Leukemia, medicine.anatomical_structure, Treatment Outcome, Rituximab, Female, RNA Interference, medicine.symptom, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.drug, Genotype, [SDV.CAN]Life Sciences [q-bio]/Cancer, Models, Biological, Lymphocyte Depletion, Diagnosis, Differential, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, microRNA, medicine, Biomarkers, Tumor, Humans, Chronic Lymphocytic Leukemia, business.industry, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, MicroRNAs, 030104 developmental biology, Immunology, biology.protein, business, Transcriptome
Abstract: International audience; The underlying in vivo mechanisms of rituximab action remain incompletely understood in chronic lymphocytic leukemia. Recent data suggest that circulating micro-ribonucleic acids correlate with chronic lymphocytic leukemia progression and response to rituximab. Our study aimed at identifying circulating micro-ribonucleic acids that predict response to rituximab monotherapy in chronic lymphocytic leukemia patients. Using a hierarchical clustering of micro-ribonucleic acid expression profiles discriminating 10 untreated patients with low or high lymphocyte counts, we found 26 micro-ribonucleic acids significantly deregulated. Using individual real-time reverse transcription polymerase chain reaction, the expression levels of micro-ribonucleic acids representative of these two clusters were further validated in a larger cohort (n=61). MiR-125b and miR-532-3p were inversely correlated with rituximab-induced lymphodepletion (P=0.020 and P=0.001, respectively) and with the CD20 expression on CD19(+) cells (P=0.0007 and P
Published: 2017

50. SET-NUP214 is a recurrent γδ lineage-specific fusion transcript associated with corticosteroid/chemotherapy resistance in adult T-ALL

Author: Aurore Touzart, Claude Preudhomme, Edouard Randriamalala, Denis Caillot, Hossein Mossafa, Aline Renneville, Alain Devidas, Vahid Asnafi, Hervé Dombret, Agata Cieslak, Elizabeth Macintyre, Bruno Lioure, Raouf Ben Abdelali, Anne Roggy, Norbert Ifrah, Thibaut Leguay, and Anne Banos
Subjects: Adult, Male, T cell, CD3, Gene Rearrangement, delta-Chain T-Cell Antigen Receptor, Immunology, Antineoplastic Agents, Drug resistance, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Biochemistry, Fusion gene, Young Adult, Adrenal Cortex Hormones, Humans, Medicine, Histone Chaperones, Oncogene Fusion, biology, Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor, business.industry, T-cell receptor, Receptors, Antigen, T-Cell, gamma-delta, Cell Biology, Hematology, Gene rearrangement, Middle Aged, DNA-Binding Proteins, Nuclear Pore Complex Proteins, medicine.anatomical_structure, Fusion transcript, Drug Resistance, Neoplasm, Adult Acute Lymphoblastic Leukemia, biology.protein, Female, business, Transcription Factors
Abstract: The SET-NUP214 (TAF1/CAN) fusion gene is a rare genetic event in T-cell acute lymphoblastic leukemia (T-ALL). Eleven (6%) of 196 T-ALL patients enrolled in the French Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) 2003 and 2005 trials harbored a SET-NUP214 transcript. SET-NUP214-positive patients were predominantly (10 [91%] of 11) T-cell receptor (TCR)-negative and strikingly associated with TCRγδ lineage T-ALLs, as defined by expression of TCRγδ, TCRδ and/or TCRγ rearrangements but no complete TCRβ variable diversity joining rearrangement in surface CD3/TCR-negative cases. When compared with SET-NUP214-negative patients, SET-NUP214-positive patients showed a significantly higher rate of corticosteroid resistance (91% vs 44%; P = .003) and chemotherapy resistance (100% vs 44%; P = .0001). All SET-NUP214-positive patients but one achieved complete remission, and 9 were allografted. Despite the poor early-treatment sensitivity, the outcome of SET-NUP214-positive patients was similar to that of SET-NUP214-negative patients.
Published: 2014

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