182 results on '"E. Bachy"'
Search Results
2. S210: CAR T-CELLS ASSOCIATED ACUTE TOXICITY IN B-CELL NON-HODGKIN LYMPHOMA: REAL-WORLD STUDY FROM THE DESCAR-T REGISTRY
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P. SESQUES, R. DI BLASI, S. LE GOUILL, G. CARTRON, G. MANSON, D. BEAUVAIS, F. LE BRAS, F. X. GROS, S. CHOQUET, P. BORIES, M. T. RUBIO, R. O. CASASNOVAS, L. BOUNAIX, M. MOHTY, M. JORIS, J. ABRAHAM, C. CASTILLA LLORENTE, M. LOSCHI, S. CARRAS, A. CHAUCHET, L. DRIEU LA ROCHELLE, J. ZERBIT, O. HERMINE, S. GUIDEZ, T. GASTINNE, J. J. TUDESQ, P. FOGARTY, F. BROUSSAIS, F. MORSCHHAUSER, R. HOUOT, C. THIEBLEMONT, and E. BACHY
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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3. S212: PHASE I STUDY OF YTB323, A CHIMERIC ANTIGEN RECEPTOR (CAR)-T CELL THERAPY MANUFACTURED USING T-CHARGE™, IN PATIENTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA
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M. Dickinson, M. Kwon, J. Briones, U. Jäger, K. Kato, E. Bachy, D. Blaise, N. Boissel, N. Shah, M Frigault, P. Riedell, L. Shune, T. Teshima, X. Zhu, E. Orlando, L. Yi, J. Davis, E. Bleickardt, I. Flinn, and P. Barba
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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4. S217: PRELIMINARY ANALYSIS OF THE PHASE II STUDY USING TOLINAPANT (ASTX660) MONOTHERAPY IN 98 PERIPHERAL T-CELL LYMPHOMA AND 51 CUTANEOUS T-CELL LYMPHOMA SUBJECTS WITH RELAPSED REFRACTORY DISEASE.
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J.-M. Michot, A. Mehta, F. Samaniego, E. Bachy, P. L. Zinzani, A. Prica, G. P. Colins, V Ribrag, N. Wagner-Johnston, D. El-Sharkawi, O. A. O’Connor, R. Wilcox, L. Wang, L. Wilson, M. Sims, J. A. Taylor, H. N. Keer, and F. Foss
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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5. S260: A MATCHED COMPARISON OF TISAGENLECLEUCEL AND AXICABTAGENE CILOLEUCEL CAR T CELLS IN RELAPSED OR REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA: A REAL-LIFE LYSA STUDY FROM THE FRENCH DESCAR-T REGISTRY
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E. Bachy, S. Le Gouill, P. Sesques, R. Di Blasi, M. Guillaume, G. Cartron, D. Beauvais, L. Roulin, F. X. Gros, M. T. Rubio, P. Bories, J. O. Bay, C. Castilla Llorente, S. Choquet, R.-O. Casasnovas, M. Mothy, S. Guidez, M. Joris, M. Loschi, S. Carras, J. Abraham, A. Chauchet, L. Drieu La Rochelle, J. Zerbit, O. Hermine, T. Gastinne, J. J. Tudesq, E. Gat, F. Broussais, C. Thieblemont, R. Houot, and F. Morschhauser
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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6. P1133: SUB-CUTANEOUS RITUXIMAB INDUCTION FOLLOWED BY SHORT RITUXIMAB MAINTENANCE IMPROVES PFS IN PATIENTS WITH LOW-TUMOR BURDEN FOLLICULAR LYMPHOMA. FINAL RESULTS OF FLIRT PHASE III TRIAL, A LYSA STUDY.
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G. Cartron, MD, PhD, E. Bachy, MD, PhD, H. Tilly, MD, N. Daguindau, MD, G.-M. Pica, MD, F. Bijou, MD, C. Mounier, MD, A. M. Clavert, MD, G. L. Damaj, MD, PhD, B. Slama, MD, O. Casasnovas, MD, R. Houot, MD, PhD, K. Bouabdallah, MD, D. Sibon, MD, PhD, O. Fitoussi, MD, N. Morineau, MD, C. Herbaux, MD, PhD, T. Gastinne, MD, L.-M. Fornecker, MD, C. Haioun, MD, PhD, V. Launay, MD, C. Araujo, MD, O. Benbrahim, MD, L. Sanhes, MD, R. Gressin, MD, H. Gonzalez, MD, F. Morschhauser, MD, PhD, L. Xerri, MD, PhD, K. Tarte, PhD, and D. Pranger, MD
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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7. P1239: TISLELIZUMAB, A PD-1 INHIBITOR FOR RELAPSED/REFRACTORY MATURE T- AND NK-CELL NEOPLASMS: RESULTS FROM A PHASE 2 STUDY
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E. Bachy, K. J. Savage, H. Huang, Y. L. Kwong, G. Gritti, Q. Zhang, A. M. Liberati, J. Cao, H. Yang, S. Hao, J. Hu, K. Zhou, F. Russo, H. Zhang, W. Sang, J. Ji, A. J. M. Ferreri, G. L. Damaj, H. Liu, W. Zhang, X. Ke, C. Ghiggi, S. Huang, X. Li, H. Yao, J. Paik, W. Novotny, W. Zhou, H. Zhu, J. Huang, and P. L. Zinzani
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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8. The upper ECHELON against T-cell lymphoma
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E. Bachy and G. Salles
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Oncology ,Hematology - Published
- 2022
9. S216: CLINICAL ACTIVITY OF CC-99282, A CEREBLON E3 LIGASE MODULATOR (CELMOD) AGENT, IN PATIENTS (PTS) WITH RELAPSED/REFRACTORY NON-HODGKIN LYMPHOMA (R/R NHL) – RESULTS FROM A PHASE 1, OPEN-LABEL STUDY
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J.-M. Michot, J. C. Chavez, C Carpio, S. Ferrari, T. A. Feldman, D. Morillo, J. Kuruvilla, A. Pinto, V. Ribrag, E Bachy, T. J. Buchholz, S. Carrancio, W.-C. Chou, C. Guarinos, F. Wu, S. Li, P. Patah, M. Pourdehnad, and L. Nastoupil
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Hematology - Published
- 2022
10. ATEZOLIZUMAB + OBINUTUZUMAB + VENETOCLAX IN PATIENTS WITH RELAPSED OR REFRACTORY MARGINAL ZONE LYMPHOMA: PRIMARY ANALYSIS OF A PHASE 2 TRIAL FROM LYSA
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C. Herbaux, J. M. Schiano de Colella, C. Thieblemont, S. Guidez, L. Ysebaert, H. Tilly, S. Gouill, R. Houot, E. Bachy, C. Laurent, G. Damaj, P. Feugier, N. Morineau, K. Tarte, F. Morschhauser, and G. Cartron
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Cancer Research ,Oncology ,Hematology ,General Medicine - Published
- 2021
11. SAFETY AND EFFICACY OF ZANUBRUTINIB IN PATIENTS WITH RELAPSED/REFRACTORY MARGINAL ZONE LYMPHOMA (MAGNOLIA PHASE 2 STUDY)
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J. Trotman, A. Tedeschi, K. Linton, P. McKay, B. Hu, H. Chan, J. Jin, M. Sobieraj‐Teague, P. L. Zinzani, M. Coleman, P. Browett, X. Ke, M. Sun, R. Marcus, C. Portell, C. Thieblemont, K. Zhou, A. M. Liberati, E. Bachy, F. Cavallo, Rég. Costello, S. Iyengar, R. Marasca, H. Mociková, J. S. Kim, D. Talaulikar, M. Co, W. Zhou, J. Huang, and S. Opat
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Oncology ,Cancer Research ,medicine.medical_specialty ,Manchester Cancer Research Centre ,business.industry ,ResearchInstitutes_Networks_Beacons/mcrc ,Marginal zone lymphoma ,Phases of clinical research ,Hematology ,General Medicine ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,Relapsed refractory ,medicine ,Indolent Non-Hodgkin Lymphoma ,In patient ,business - Abstract
Background: BCR signaling mediated through Bruton's tyrosine kinase (BTK) plays a critical role in the development and maintenance of marginal zone lymphoma (MZL). BTK inhibitors have established activity in relapsed/refractory (R/R) MZL with the phase 2 study of ibrutinib demonstrating an objective response rate (ORR) of 48% (Noy et al. Blood. 2017;129:2224-2232).
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- 2021
12. Thromboembolic events and thromboprophylaxis associated with immunomodulators in multiple myeloma patients: a real-life study
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V, Leclerc, L, Karlin, C, Herledan, L, Marchal, A, Baudouin, A, Gouraud, A G, Caffin, V, Larbre, A, Lazareth, E, Bachy, G, Salles, H, Ghesquières, C, Rioufol, and F, Ranchon
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Anticoagulants ,Humans ,Immunologic Factors ,Venous Thromboembolism ,Multiple Myeloma ,Retrospective Studies - Abstract
The aim of this study is to assess international guidelines implementation concerning thromboprophylaxis strategy in myeloma patients treated with immunomodulatory drugs.This retrospective study includes multiple myeloma patients treated with immunomodulatory drugs between 2014 and 2017 in the Hematology department of a teaching hospital (Hospices Civils de Lyon, France) and followed by the multidisciplinary care plan for cancer outpatients ONCORAL (ONCological care for outpatients with ORAL anticancer drugs). Data from immunomodulatory drugs administration, thromboprophylaxis strategy and thrombotic events were collected from medical files. Adherence to 2010 International Myeloma Working Group (IMWG) guidelines was assessed.213 patients received at least one immunomodulatory drug: lenalidomide (60.9%), pomalidomide (24.0%) and thalidomide (15.1%). About two third of treatment lines (66.2%) were in accordance with IMWG recommendations. Among the others, 30.5% and 69.5% had thromboprophylaxis, respectively, superior or inferior to IMWG recommendations. 37 venous thrombotic events and 4 arterial thromboembolisms (one patient experienced both a stroke and deep venous thrombosis simultaneously) were reported.Thromboprophylaxis was systematically performed in myeloma patients treated with immunomodulatory drugs in this real-life retrospective cohort. However, the choice of anticoagulant or anti-platelet agent remains debatable, as adherence to existing guidelines was variable.
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- 2021
13. PCN10 A MATCH-ADJUSTED INDIRECT TREATMENT COMPARISON (MAIC) OF LENALIDOMIDE PLUS RITUXIMAB (R2) VERSUS RITUXIMAB PLUS CHEMOTHERAPY (R-CHEMO) FOR RELAPSED AND/OR REFRACTORY (R/R) FOLLICULAR LYMPHOMA (FL)
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F. Hernandez-Ilizaliturri, S. Abouzaid, C. Parker, A. Tabah, L. Arcaini, E. Bachy, C. Fox, C.L. Watkins, and J. Jones
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Oncology ,medicine.medical_specialty ,Chemotherapy ,business.industry ,Health Policy ,medicine.medical_treatment ,Public Health, Environmental and Occupational Health ,Follicular lymphoma ,medicine.disease ,Refractory ,Indirect Treatment ,Internal medicine ,medicine ,Rituximab ,business ,Lenalidomide ,medicine.drug - Published
- 2019
14. ABVD (8 cycles) versus BEACOPP (4 escalated cycles ≥4 baseline): final results in stage III–IV low-risk Hodgkin lymphoma (IPS 0–2) of the LYSA H34 randomized trial
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N, Mounier, P, Brice, S, Bologna, J, Briere, I, Gaillard, M, Heczko, J, Gabarre, O, Casasnovas, J, Jaubert, P, Colin, A, Delmer, A, Devidas, E, Bachy, E, Nicolas-Virelizier, A, Aoudjhane, C, Humbrecht, M, Andre, P, Carde, and J M, Pignon
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Adult ,Male ,BEACOPP ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Vinblastine ,law.invention ,Bleomycin ,Young Adult ,Randomized controlled trial ,law ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Clinical endpoint ,Humans ,Progression-free survival ,Cyclophosphamide ,Survival analysis ,Etoposide ,Neoplasm Staging ,Dose-Response Relationship, Drug ,business.industry ,Hazard ratio ,Hematology ,Middle Aged ,Hodgkin Disease ,Survival Analysis ,Surgery ,Dacarbazine ,Regimen ,Treatment Outcome ,Oncology ,ABVD ,Doxorubicin ,Vincristine ,Procarbazine ,Prednisone ,Female ,business ,medicine.drug - Abstract
Background: Treatment with escalated BEACOPP achieved a superior time to treatment failure over ABVD in patients with disseminated Hodgkin lymphoma. However, recent clinical trials have failed to confirm BEACOPP overall survival (OS) superiority over ABVD. In addition, the gain in low-risk patients is still a matter of debate. Patients and methods: We randomly compared ABVD (8 cycles) with BEACOPP (escalated 4 cycles ≥baseline 4 cycles) in low-risk patients with an International Prognostic Score (IPS) of 0-2. The primary end point was event-free survival (EFS). This parallel group, open-label phase 3 trial was registered under #RECF0219 at French National Cancer Institute. Results: One hundred and fifty patients were randomized in this trial (ABVD 80, BEACOPP 70): 28 years was the median age, 50% were male and IPS was 0-1 for 64%. Complete remission rate was 85% for ABVD and 90% for BEACOPP. Progression or relapses were more frequent in the ABVD patients than in the BEACOPP patients (17 versus 5 patients). With a median follow-up period of 5.5 years, seven patients died: six in the ABVD arm and one in the BEACOPP arm (HL 3 and 0, 2nd cancer 2 and 1, accident 1 and 0). The EFS at 5 years was estimated at 62% for ABVD versus 77%, for BEACOPP [hazards ratio (HR) = 0.6, P = 0.07]. The progression-free survival (PFS) at 5 years was 75% versus 93% (HR = 0.3, P=0.007). The OS at 5 years was 92% versus 99% (HR = 0.18, P = 0.06). Conclusion: Fewer progressions/relapses were observed with BEACOPP, demonstrating the high efficacy of the more intensive regimen, even in low-risk patients. However, additional considerations, balancing treatment-related toxicity and late morbidity due to salvage may help with decision-making with regard to treatment with ABVD or BEACOPP. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
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- 2014
15. A matched case-control study of toxoplasmosis after allogeneic haematopoietic stem cell transplantation: still a devastating complication
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A. Conrad, M. Le Maréchal, D. Dupont, S. Ducastelle-Leprêtre, M. Balsat, H. Labussière-Wallet, F. Barraco, F.-E. Nicolini, X. Thomas, L. Gilis, C. Chidiac, T. Ferry, F. Wallet, M. Rabodonirina, G. Salles, M. Michallet, F. Ader, E. Bachy, N. Benech, A.-L. Bienvenu, G. Billaud, F. Biron, A. Boibieux, O. Dumitrescu, V. Escuret, G. Fossard, E. Frobert, S. Goutelle, A. Grateau, Y. Guillermin, M. Heiblig, L. Lebras, B. Lina, G. Lina, P. Miailhes, A.-S. Michallet, M.-C. Michallet, G. Monneret, F. Morfin-Sherpa, T. Perpoint, M. Peyrouse de Montclos, S. Picot, F. Poitevin-Later, A. Quintela, S. Roux, J. Saison, C. Sarkozy, A. Sénéchal, M. Sobh, F. Valour, M. Wallon, E. Wattel, Pathogenèse des légionelles- Legionella pathogenesis (LegioPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Institut de parasitologie et mycologie médicale, Hospices Civils de Lyon (HCL), Team Waking [Lyon], Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Laboratoire des pathogènes émergents -- Emerging Pathogens Laboratory (LPE-Fondation Mérieux), Réanimation Médicale et Chirurgicale [Centre Hospitalier Lyon-Sud], Laboratoire de Parasitologie et Mycologie, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Integrated Physiology of the Brain Arousal Systems (WAKING), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL)
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0301 basic medicine ,Male ,isolation & purification ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Etanercept ,0302 clinical medicine ,Risk Factors ,Epidemiology ,80 and over ,Odds Ratio ,Medicine ,030212 general & internal medicine ,Lung ,Aged, 80 and over ,education.field_of_study ,Mortality rate ,Hematopoietic Stem Cell Transplantation ,General Medicine ,Syndrome ,Middle Aged ,3. Good health ,Infectious Diseases ,Treatment Outcome ,Female ,epidemiology ,France ,Infection ,Toxoplasma ,Toxoplasmosis ,Microbiology (medical) ,Risk ,Homologous ,Adult ,medicine.medical_specialty ,Consensus ,Patients ,030106 microbiology ,Population ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,03 medical and health sciences ,Necrosis ,Internal medicine ,Transplantation, Homologous ,Humans ,education ,Aged ,Transplantation ,business.industry ,Case-control study ,Odds ratio ,mortality ,Survival Analysis ,Surgery ,Case-Control Studies ,adverse effects ,pathology ,business ,Complication ,Stem Cell Transplantation - Abstract
International audience; Toxoplasmosis (TXP) is a life-threatening complication of allogeneic haematopoietic stem cell transplantation (AHSCT). Little is known about the risk factors and there is no consensus on prophylactic measures. To investigate the risk factors, we conducted a single-centre, retrospective matched case-control study among adults who underwent AHSCT from January 2006 to March 2015 in our hospital. TXP cases were identified from the prospectively maintained hospital's database. The 1:2 control population consisted of the two patients who received an AHSCT immediately before and after each case with similar donor relationship (related, unrelated) but who did not develop TXP. Risk factors were identified by conditional logistic regression. Clinical features and outcome of TXP were examined. Twenty-three (3.9%) cases of TXP (20 diseases, three infections) were identified among 588 AHSCT recipients. Twenty (87%) cases had a positive pre-transplant Toxoplasma gondii serology. In comparison with 46 matched control patients, risk factors were the absence of effective anti-Toxoplasma prophylaxis (odds ratio (OR) 11.95; 95% CI 3.04-46.88; p \textless0.001), high-grade (III-IV) acute graft-versus-host-disease (OR 3.1; 95% CI 1.04-9.23; p 0.042) and receipt of the tumour necrosis factor-alpha blocker etanercept (OR 12.02; 95% CI 1.33-108.6; p 0.027). Mortality attributable to TXP was 43.5% (n = 10). Non-relapse mortality rates during the study period of cases and controls were 69.6% (n = 16) and 17.4% (n = 8), respectively. Lung involvement was the dominant clinical feature (n = 14). Two cases were associated with graft failure, one preceded by haemophagocytic syndrome. Given TXP-related morbidity and attributable mortality, anti-Toxoplasma prophylaxis is essential for optimized management of seropositive AHSCT recipients
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- 2016
16. Comparative toxicities of 3 platinum-containing chemotherapy regimens in relapsed/refractory lymphoma patients
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F, Tixier, F, Ranchon, A, Iltis, N, Vantard, V, Schwiertz, E, Bachy, F, Bouafia-Sauvy, C, Sarkozy, J F, Tournamille, E, Gyan, G, Salles, and C, Rioufol
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Adult ,Aged, 80 and over ,Male ,Adolescent ,Lymphoma ,Middle Aged ,Young Adult ,Drug Resistance, Neoplasm ,Recurrence ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Female ,Kidney Diseases ,Aged ,Platinum ,Retrospective Studies - Abstract
Optimal salvage chemotherapy regimen for patients with relapsed or refractory Hodgkin and non-Hodgkin lymphoma remains unclear but often based on platinum regimens. This retrospective study assesses in real life the toxicities profiles of patients with relapsed or refractory lymphoma treated with DHA (dexamethasone, high dose aracytine cytarabine) plus platinum salt (dexamethasone-High dose aracytine (cis)platin (DHAP), dexamethasone-High dose aracytine carboplatin (DHAC), or dexamethasone-High dose aracytine Oxaliplatin (DHAOX)), from February 2007 to May 2013 in 2 French hospitals. Toxicities were recorded from medical files and assessed according to the National Cancer Institute Common Toxicity Criteria version 3.0. Potential risk factors of renal insufficiency were tested by univariate analyses. A total of 276 patients were treated: 168 with DHAP (60.9%), 79 with DHAOX (28.6%), and 29 with DHAC (10.5%). Rituximab was associated in 80.1% of patients (n = 221). Renal failure was reported in 97 patients, mainly with cisplatin regimen (86.6%) leading to 8.9% grade III to IV renal failure (P = .001). Renal insufficiency was reversible in most patients but remained persistent in 24, with all of them being treated with DHAP except 1. Cisplatin-based regimen (50.0% versus 12.0%, P .05) and female (44.6% versus 29.7%, P .05) appeared to be at higher risks of renal failure. Platinum cumulative dose is a significant risk factor of nephrotoxicity. Hematologic toxicity was more frequent with carboplatin and cisplatin with at least 1 event (all toxicity grade) respectively in 79.3% and 71.4% of patients treated (P .005). Auditory toxicity was mainly reported with cisplatin (n = 19; 4 grade I-II and 15 grade III-IV). Oxaliplatin was implicated in 77.6% of neurotoxicity (n = 59), mainly moderate (grade I-II). In conclusion, DHAOX and DHAC regimens have more favorable toxicity profile than DHAP regimen. Their lack of renal toxicity makes them attractive regimens, which may be interesting for patients eligible for autologous stem cell transplantation. Nevertheless, these results have to be confirmed by the therapeutic efficacy of these 3 regimens.
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- 2016
17. CHARACTERISTICS AND OUTCOMES OF RELAPSED FOLLICULAR LYMPHOMA AFTER AUTOLOGOUS STEM CELL TRANSPLANTATION IN THE RITUXIMAB ERA
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P. Sesques, C. Golfier, J. Boursier, E. Bachy, A. Traverse-Glehen, S. Le Gouill, O. Casasnovas, H. Ghesquieres, and G. Salles
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Cancer Research ,Oncology ,Hematology ,General Medicine - Published
- 2017
18. Le pourcentage de macrophages et le nombre des mastocytes et lymphocytes TiA1+sont des biomarqueurs du caractère réfractaire primaire ou d’une rechute précoce dans les lymphomes de Hodgkin classiques
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Richard Delarue, Nicole Brousse, Vincent Ribrag, E. Bachy, V. Vasiliu, Danielle Canioni, Jacques Bosq, Olivier Hermine, Julie Bruneau, Bénédicte Deau, Bruno Varet, and Marie-Thérèse Rubio
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Pathology and Forensic Medicine - Published
- 2011
19. Optimizing drug combinations for T-PLL: restoring DNA damage and P53-mediated apoptotic responses.
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von Jan J, Timonen S, Braun T, Jiang Q, Ianevski A, Peng Y, McConnell K, Sindaco P, Müller TA, Pützer S, Klepzig H, Jungherz D, Dechow A, Wahnschaffe L, Giri AK, Kankainen M, Kuusanmäki H, Neubauer HA, Moriggl R, Mazzeo P, Schmidt N, Koch R, Hallek M, Chebel A, Armisen D, Genestier L, Bachy E, Mishra A, Schrader A, Aittokallio T, Mustjoki S, and Herling M
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- Humans, Animals, Mice, Antineoplastic Combined Chemotherapy Protocols pharmacology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bridged Bicyclo Compounds, Heterocyclic pharmacology, Bridged Bicyclo Compounds, Heterocyclic therapeutic use, Histone Deacetylase Inhibitors pharmacology, Histone Deacetylase Inhibitors therapeutic use, Sulfonamides pharmacology, Xenograft Model Antitumor Assays, Proto-Oncogene Proteins c-mdm2 metabolism, Proto-Oncogene Proteins c-mdm2 genetics, Proto-Oncogene Proteins c-mdm2 antagonists & inhibitors, Tumor Suppressor Protein p53 metabolism, Tumor Suppressor Protein p53 genetics, Apoptosis drug effects, DNA Damage drug effects, Leukemia, Prolymphocytic, T-Cell drug therapy, Leukemia, Prolymphocytic, T-Cell genetics, Leukemia, Prolymphocytic, T-Cell metabolism, Leukemia, Prolymphocytic, T-Cell pathology
- Abstract
Abstract: T-prolymphocytic leukemia (T-PLL) is a mature T-cell neoplasm associated with marked chemotherapy resistance and continued poor clinical outcomes. Current treatments, that is, the CD52-antibody alemtuzumab, offer transient responses, with relapses being almost inevitable without consolidating allogeneic transplantation. Recent more detailed concepts of T-PLL's pathobiology fostered the identification of actionable vulnerabilities: (1) altered epigenetics, (2) defective DNA damage responses, (3) aberrant cell-cycle regulation, and (4) deregulated prosurvival pathways, including T-cell receptor and JAK/STAT signaling. To further develop related preclinical therapeutic concepts, we studied inhibitors of histone deacetylases ([H]DACs), B-cell lymphoma 2 (BCL2), cyclin-dependent kinase (CDK), mouse double minute 2 (MDM2), and classical cytostatics, using (1) single-agent and combinatorial compound testing in 20 well-characterized and molecularly profiled primary T-PLL (validated by additional 42 cases) and (2) 2 independent murine models (syngeneic transplants and patient-derived xenografts). Overall, the most efficient/selective single agents and combinations (in vitro and in mice) included cladribine, romidepsin ([H]DAC), venetoclax (BCL2), and/or idasanutlin (MDM2). Cladribine sensitivity correlated with expression of its target RRM2. T-PLL cells revealed low overall apoptotic priming with heterogeneous dependencies on BCL2 proteins. In additional 38 T-cell leukemia/lymphoma lines, TP53 mutations were associated with resistance toward MDM2 inhibitors. P53 of T-PLL cells, predominantly in wild-type configuration, was amenable to MDM2 inhibition, which increased its MDM2-unbound fraction. This facilitated P53 activation and downstream signals (including enhanced accessibility of target-gene chromatin regions), in particular synergy with insults by cladribine. Our data emphasize the therapeutic potential of pharmacologic strategies to reinstate P53-mediated apoptotic responses. The identified efficacies and their synergies provide an informative background on compound and patient selection for trial designs in T-PLL., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
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- 2024
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20. Glofitamab in Relapsed/Refractory Mantle Cell Lymphoma: Results From a Phase I/II Study.
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Phillips TJ, Carlo-Stella C, Morschhauser F, Bachy E, Crump M, Trněný M, Bartlett NL, Zaucha J, Wrobel T, Offner F, Humphrey K, Relf J, Filézac de L'Etang A, Carlile DJ, Byrne B, Qayum N, Lundberg L, and Dickinson M
- Abstract
Purpose: Patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) have a poor prognosis. The phase I/II NP30179 study (ClinicalTrials.gov identifier: NCT03075696) evaluated glofitamab monotherapy in patients with R/R B-cell lymphomas, with obinutuzumab pretreatment (Gpt) to mitigate the risk of cytokine release syndrome (CRS) with glofitamab. We present data for patients with R/R MCL., Methods: Eligible patients with R/R MCL (at least one previous therapy) received Gpt (1,000 or 2,000 mg) 7 days before the first glofitamab dose (single dose or split over 2 days if required). Glofitamab step-up dosing was administered once a day on days 8 (2.5 mg) and 15 (10 mg) of cycle 1, with a target dose of 16 or 30 mg once every 3 weeks from cycle 2 day 1 onward, for 12 cycles. Efficacy end points included investigator-assessed complete response (CR) rate, overall response rate (ORR), and duration of CR., Results: Of 61 enrolled patients, 60 were evaluable for safety and efficacy. Patients had received a median of two previous therapies (range, 1-5). CR rate and ORR were 78.3% (95% CI, 65.8 to 87.9) and 85.0% (95% CI, 73.4 to 92.9), respectively. In patients who had received previous treatment with a Bruton tyrosine kinase inhibitor (n = 31), CR rate was 71.0% (95% CI, 52.0 to 85.8) and ORR was 74.2% (95% CI, 55.4 to 88.1). CRS after glofitamab administration occurred in 70.0% of patients, with a lower incidence in the 2,000 mg (63.6% [grade ≥2, 22.7%]) versus 1,000 mg (87.5%; grade ≥2, 62.5%) Gpt cohort. Four adverse events led to glofitamab withdrawal (all infections)., Conclusion: Fixed-duration glofitamab induced high CR rates in heavily pretreated patients with R/R MCL; the safety profile was manageable with appropriate support.
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- 2024
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21. 18F-FDG PET/CT metrics-based stratification of large B-cell lymphoma receiving CAR-T cell therapy: immunosuppressive tumor microenvironment as a negative prognostic indicator in patients with high tumor burden.
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Sheng LS, Shen R, Yan ZX, Wang C, Zheng X, Zhang YL, Yang HX, Wu W, Xu PP, Cheng S, Bachy E, Sesques P, Jacquet-Francillon N, Jiang XF, Zhao WL, and Wang L
- Abstract
Chimeric antigen receptor T (CAR-T) cell therapy has greatly improved the prognosis of relapsed and refractory patients with large B-cell lymphoma (LBCL). Early identification and intervention of patients who may respond poorly to CAR-T cell therapy will help to improve the efficacy. Ninety patients from a Chinese cohort who received CAR-T cell therapy and underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scans at the screening stage (median time to infusion 53.5 days, range 27-176 days), 1 month and 3 months after CAR-T cell infusion were analyzed, with RNA-sequencing conducted on 47 patients at the screening stage. Patients with maximum diameter of the largest lesion (Dmax) < 6 cm (N = 60) at screening stage showed significantly higher 3-month complete response rate (85.0% vs. 33.3%, P < 0.001), progression-free survival (HR 0.17; 95% CI 0.08-0.35, P < 0.001) and overall survival (HR 0.18; 95% CI 0.08-0.40, P < 0.001) than those with Dmax ≥ 6 cm (N = 30). Besides, at the screening stage, Dmax combined with extranodal involvement was more efficient in distinguishing patient outcomes. The best cut-off values for total metabolic tumor volume (tMTV) and total lesion glycolysis (tTLG) at the screening stage were 50cm
3 and 500 g, respectively. A prediction model combining maximum standardized uptake value (SUVmax) at 1 month after CAR-T cell therapy (M1) and tTLG clearance rate was established to predict early progression for partial response/stable disease patients evaluated at M1 after CAR-T cell therapy and validated in Lyon cohort. Relevant association of the distance separating the two farthest lesions, standardized by body surface area to the severity of neurotoxicity (AUC = 0.74; P = 0.034; 95% CI, 0.578-0.899) after CAR-T cell therapy was found in patients received axicabtagene ciloleucel. In patients with Dmax ≥ 6 cm, RNA-sequencing analysis conducted at the screening stage showed enrichment of immunosuppressive-related biological processes, as well as increased M2 macrophages, cancer-associated fibroblasts, myeloid-derived suppressor cells, and intermediate exhausted T cells. Collectively, immunosuppressive tumor microenvironment may serve as a negative prognostic indicator in patients with high tumor burden who respond poorly to CAR-T cell therapy., (© 2024. The Author(s).)- Published
- 2024
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22. Etoposide addition and brentuximab vedotin consolidation in first-line treatment of CD30-positive peripheral T-cell lymphoma: can we improve BV-CHP?
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Julia E and Bachy E
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- Humans, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Male, Female, Middle Aged, Consolidation Chemotherapy, Brentuximab Vedotin therapeutic use, Lymphoma, T-Cell, Peripheral drug therapy, Etoposide therapeutic use, Ki-1 Antigen metabolism
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- 2024
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23. CAR T-cells in very elderly (≥80 years) lymphoma patients: a DESCAR-T analysis.
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Menez S, Bourbon E, Gounot R, Tudesq JJ, Moya N, Houot R, and Bachy E
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- 2024
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24. Safety and efficacy of odronextamab in patients with relapsed or refractory follicular lymphoma.
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Kim TM, Taszner M, Novelli S, Cho SG, Villasboas JC, Merli M, Jiménez-Ubieto A, Tessoulin B, Poon LM, Tucker D, Walewski J, Yi S, Song Y, Chong G, Bachy E, Guidez S, Alonso A, Jagadeesh D, Zhang W, Magnano L, Iskierka-Jażdżewska E, Tani M, Shen B, Uppala A, Zhu M, Shariff S, Brouwer-Visser J, Chaudhry A, Mohamed H, Ambati S, and Luminari S
- Abstract
Background: Odronextamab, a CD20×CD3 bispecific antibody that engages cytotoxic T cells to destroy malignant B cells, has demonstrated encouraging activity across multiple subtypes of relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma., Patients and Methods: This phase II study (ELM-2; NCT03888105) evaluated odronextamab in patients with R/R follicular lymphoma after two or more lines of systemic therapy. Patients received intravenous odronextamab in 21-day cycles, with step-up dosing in cycle 1 to help mitigate the risk of cytokine release syndrome, until disease progression or unacceptable toxicity. The primary endpoint was objective response rate by independent central review., Results: Among 128 patients evaluated, 95% completed cycle 1, and 85% completed four or more cycles. At 20.1 months' efficacy follow-up, objective response rate was 80.0% and complete response rate was 73.4%. Median duration of complete response was 25.1 months. Median progression-free survival was 20.7 months, and median overall survival was not reached. Discontinuation of odronextamab due to adverse events occurred in 16% of patients. The most common treatment-emergent adverse events were cytokine release syndrome [56%; grade ≥3 1.7% (1/60) with 0.7/4/20 mg step-up], neutropenia (39%), and pyrexia (38%)., Conclusions: Odronextamab achieved high complete response rates with generally manageable safety in patients with heavily pretreated R/R follicular lymphoma., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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25. Novel prognostic scoring systems for severe CRS and ICANS after anti-CD19 CAR T cells in large B-cell lymphoma.
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Sesques P, Kirkwood AA, Kwon M, Rejeski K, Jain MD, Di Blasi R, Brisou G, Gros FX, le Bras F, Bories P, Choquet S, Rubio MT, Iacoboni G, O'Reilly M, Casasnovas RO, Bay JO, Mohty M, Joris M, Abraham J, Castilla Llorente C, Loschi M, Carras S, Chauchet A, La Rochelle LD, Hermine O, Guidez S, Cony-Makhoul P, Fogarty P, Le Gouill S, Morschhauser F, Gastinne T, Cartron G, Subklewe M, Locke FL, Sanderson R, Barba P, Houot R, and Bachy E
- Subjects
- Humans, Male, Female, Middle Aged, Prognosis, Aged, Adult, Neurotoxicity Syndromes etiology, Biological Products therapeutic use, Biological Products adverse effects, France, Aged, 80 and over, Receptors, Antigen, T-Cell, Immunotherapy, Adoptive adverse effects, Immunotherapy, Adoptive methods, Antigens, CD19 immunology, Lymphoma, Large B-Cell, Diffuse therapy, Lymphoma, Large B-Cell, Diffuse immunology, Cytokine Release Syndrome etiology
- Abstract
Autologous anti-CD19 chimeric antigen receptor (CAR) T cells are now used in routine practice for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Severe (grade ≥ 3) cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) are still the most concerning acute toxicities leading to frequent intensive care unit (ICU) admission, prolonging hospitalization, and adding significant cost to treatment. We report on the incidence of CRS and ICANS and the outcomes in a large cohort of 925 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) in France based on patient data captured through the DESCAR-T registry. CRS of any grade occurred in 778 patients (84.1%), with 74 patients (8.0%) with grade 3 CRS or higher, while ICANS of any grade occurred in 375 patients (40.5%), with 112 patients (12.1%) with grade ≥ 3 ICANS. Based on the parameters selected by multivariable analyses, two independent prognostic scoring systems (PSS) were derived, one for grade ≥ 3 CRS and one for grade ≥ 3 ICANS. CRS-PSS included bulky disease, a platelet count < 150 G/L, a C-reactive protein (CRP) level > 30 mg/L and no bridging therapy or stable or progressive disease (SD/PD) after bridging. Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade ≥ 3 CRS. ICANS-PSS included female sex, low level of platelets (< 150 G/L), use of axi-cel and no bridging therapy or SD/PD after bridging. Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade ≥ 3 ICANS. Both scores were externally validated in international cohorts of patients treated with tisa-cel or axi-cel., (© 2024. The Author(s).)
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- 2024
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26. A Cost-Effectiveness Analysis of Axicabtagene Ciloleucel versus Tisagenlecleucel in the Treatment of Diffuse Large B-cell Lymphoma Based on a Real-World French Registry.
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Ray M, Castaigne JG, Zang A, Patel A, Hancock E, Brighton N, and Bachy E
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- Humans, Male, France, Middle Aged, Female, Aged, Antigens, CD19 therapeutic use, Antigens, CD19 economics, Antigens, CD19 immunology, Adult, Receptors, Antigen, T-Cell therapeutic use, Cost-Effectiveness Analysis, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse therapy, Lymphoma, Large B-Cell, Diffuse economics, Cost-Benefit Analysis, Registries, Biological Products therapeutic use, Biological Products economics, Immunotherapy, Adoptive economics, Immunotherapy, Adoptive methods, Immunotherapy, Adoptive adverse effects
- Abstract
Introduction: Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are chimeric antigen receptor T-cell therapies that were evaluated in third and later line (3L+) relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) in the ZUMA-1 and JULIET trials, respectively. As of October 2021, the DESCAR-T registry included 729 French patients with 3L+ r/r DLBCL who received axi-cel or tisa-cel. Using these data, propensity score matching was used to conduct an adjusted comparison between axi-cel and tisa-cel. Axi-cel was associated with statistically significant improvements in overall survival (OS) and progression-free survival (PFS), and significantly more frequent Grade ≥ 3 immune effector cell-associated neurotoxicity syndrome (ICANS), compared with tisa-cel. There was no significant difference in Grade ≥ 3 cytokine release syndrome (CRS). The current analysis assessed the cost-effectiveness of axi-cel versus tisa-cel in the treatment of 3L+ r/r DLBCL using propensity score-matched data from the DESCAR-T registry., Methods: A partitioned survival model was used to extrapolate costs and quality-adjusted life years (QALYs) over a lifetime. Survival curves for PFS and OS were based on independent mixture cure models fitted to digitized Kaplan-Meier data for the propensity score-matched DESCAR-T populations. Average duration of intensive care unit stays for each of axi-cel and tisa-cel in DESCAR-T were used to inform adverse event costs. Selected parametric survival distributions were based on clinical expert validation. Utility values were derived from ZUMA-1, and costs were obtained from French registries and published sources. List prices were used for both axi-cel and tisa-cel. Costs and outcomes were discounted at an annual rate of 2.5%., Results: Axi-cel is associated with an incremental cost-effectiveness ratio of €15,520 per QALY compared with tisa-cel., Conclusion: Based on explicit willingness-to-pay thresholds applied in Europe, axi-cel is expected to be a cost-effective use of healthcare resources in real-world clinical settings compared with tisa-cel in 3L+ r/r DLBCL., (© 2024. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)
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- 2024
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27. Efficacy of CAR T-cell therapy is not impaired by previous bispecific antibody treatment in large B-cell lymphoma.
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Crochet G, Iacoboni G, Couturier A, Bachy E, Iraola-Truchuelo J, Gastinne T, Cartron G, Fradon T, Lesne B, Kwon M, Gounot R, Martínez-Cibrian N, Castilla-Llorente C, Abrisqueta P, Guerreiro M, Sarkozy C, Aspa-Cilleruelo JM, Camus V, Guidez S, Chauchet A, Deconinck E, Bouabdallah K, Bosch F, Barba P, Morschhauser F, and Houot R
- Subjects
- Humans, Retrospective Studies, Male, Female, Middle Aged, Aged, Receptors, Chimeric Antigen immunology, Adult, Treatment Outcome, Antibodies, Bispecific therapeutic use, Immunotherapy, Adoptive methods, Lymphoma, Large B-Cell, Diffuse therapy, Lymphoma, Large B-Cell, Diffuse immunology
- Abstract
Abstract: In this retrospective study, chimeric antigen receptor T cells remained effective in patients with relapsed/refractory large B-cell lymphoma after prior exposure to bispecific antibodies (BsAbs) targeting different antigens. These results are relevant to clinical practice, particularly given the increasing use of BsAbs in earlier treatment lines., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
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- 2024
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28. Comprehensive Genetic Profiling Reveals Frequent Alterations of Driver Genes on the X Chromosome in Extranodal NK/T-cell Lymphoma.
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Ito Y, Marouf A, Kogure Y, Koya J, Liévin R, Bruneau J, Tabata M, Saito Y, Shingaki S, Yuasa M, Yamaguchi K, Murakami K, Weil R, Vavasseur M, Andrieu GP, Latiri M, Veleanu L, Dussiot M, André I, Joshi A, Lagresle-Peyrou C, Magerus A, Chaubard S, Lavergne D, Bachy E, Brunet E, Fataccioli V, Brouzes C, Laurent C, de Leval L, Traverse-Glehen A, Bossard C, Parrens M, Meignin V, Philippe L, Rossignol J, Suarez F, Michot JM, Tournilhac O, Damaj G, Lemonnier F, Bôle-Feysot C, Nitschké P, Tesson B, Laurent C, Molina T, Asnafi V, Watatani Y, Chiba K, Okada A, Shiraishi Y, Tsukita S, Izutsu K, Miyoshi H, Ohshima K, Sakata S, Dobashi A, Takeuchi K, Sanada M, Gaulard P, Jaccard A, Ogawa S, Hermine O, Kataoka K, and Couronné L
- Subjects
- Humans, Male, Female, DNA Copy Number Variations, Mutation, Middle Aged, Animals, Adult, Mice, Prognosis, Aged, Gene Expression Profiling, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Young Adult, Epstein-Barr Virus Infections genetics, Epstein-Barr Virus Infections virology, Epstein-Barr Virus Infections complications, Chromosomes, Human, X genetics, Lymphoma, Extranodal NK-T-Cell genetics, Lymphoma, Extranodal NK-T-Cell virology, Lymphoma, Extranodal NK-T-Cell pathology, Lymphoma, Extranodal NK-T-Cell metabolism
- Abstract
Extranodal NK/T-cell lymphoma (ENKTCL) is an Epstein-Barr virus (EBV)-related neoplasm with male dominance and a poor prognosis. A better understanding of the genetic alterations and their functional roles in ENKTCL could help improve patient stratification and treatments. In this study, we performed a comprehensive genetic analysis of 178 ENKTCL cases to delineate the landscape of mutations, copy number alterations (CNA), and structural variations, identifying 34 driver genes including six previously unappreciated ones, namely, HLA-B, HLA-C, ROBO1, CD58, POT1, and MAP2K1. Among them, CD274 (24%) was the most frequently altered, followed by TP53 (20%), CDKN2A (19%), ARID1A (15%), HLA-A (15%), BCOR (14%), and MSN (14%). Chromosome X losses were the most common arm-level CNAs in females (∼40%), and alterations of four X-linked driver genes (MSN, BCOR, DDX3X, and KDM6A) were more frequent in males and females harboring chromosome X losses. Among X-linked drivers, MSN was the most recurrently altered, and its expression was lost in approximately one-third of cases using immunohistochemical analysis. Functional studies of human cell lines showed that MSN disruption promoted cell proliferation and NF-κB activation. Moreover, MSN inactivation increased sensitivity to NF-κB inhibition in vitro and in vivo. In addition, recurrent deletions were observed at the origin of replication in the EBV genome (6%). Finally, by integrating the 34 drivers and 19 significant arm-level CNAs, nonnegative matrix factorization and consensus clustering identified two molecular groups with different genetic features and prognoses irrespective of clinical prognostic factors. Together, these findings could help improve diagnostic and therapeutic strategies in ENKTCL. Significance: Integrative genetic analyses and functional studies in extranodal NK/T-cell lymphoma identify frequent disruptions of X-linked drivers, reveal prognostic molecular subgroups, and uncover recurrent MSN alterations that confer sensitivity to NF-κB inhibition., (©2024 American Association for Cancer Research.)
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- 2024
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29. Author Correction: Axicabtagene ciloleucel as second-line therapy in large B cell lymphoma ineligible for autologous stem cell transplantation: a phase 2 trial.
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Houot R, Bachy E, Cartron G, Gros FX, Morschhauser F, Oberic L, Gastinne T, Feugier P, Duléry R, Thieblemont C, Joris M, Jardin F, Choquet S, Casasnovas O, Brisou G, Cheminant M, Bay JO, Gutierrez FL, Menard C, Tarte K, Delfau MH, Portugues C, Itti E, Palard-Novello X, Blanc-Durand P, Al Tabaa Y, Bailly C, Laurent C, and Lemonnier F
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- 2024
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30. Indirect treatment comparisons: how to MAIC it right?
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Bachy E
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- 2024
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31. Evaluation of participation and recruitment bias in a prospective Real World Data in Lymphoma and Survival in Adults (REALYSA) cohort for newly diagnosed lymphoma patients over 1 year in a hematology department of teaching hospital.
- Author
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Lan CL, Belot A, Golfier C, Audin B, Sesques P, Bernier A, Safar V, Ferrant E, Lazareth A, Lequeu H, Karlin L, Ghergus D, Maarek A, Aussedat G, Idlhaj M, Salles G, Cherblanc F, Bachy E, and Ghesquieres H
- Subjects
- Humans, Prospective Studies, Male, Female, Adult, Middle Aged, Aged, Patient Selection, Survival Rate, Hematology, Lymphoma mortality, Lymphoma diagnosis, Lymphoma therapy, Hospitals, Teaching
- Published
- 2024
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32. High efficacy of CD19 CAR T cells in patients with transformed Waldenström macroglobulinemia.
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Durot E, Roos-Weil D, Chauchet A, Decroocq J, Di Blasi R, Gastinne T, Bensaber H, Cheminant M, Jacquet C, Guidez S, Gros FX, Bachy E, Coste A, Cony-Makhoul P, Treon SP, Delmer A, Reshef R, Le Gouill S, Castillo JJ, and Houot R
- Subjects
- Humans, Male, Aged, Female, Middle Aged, Receptors, Chimeric Antigen immunology, T-Lymphocytes immunology, T-Lymphocytes pathology, Treatment Outcome, Waldenstrom Macroglobulinemia therapy, Waldenstrom Macroglobulinemia immunology, Waldenstrom Macroglobulinemia pathology, Immunotherapy, Adoptive methods, Antigens, CD19 immunology
- Abstract
Abstract: Histologic transformation of Waldenström macroglobulinemia (HT-WM) carries a poor prognosis with standard treatments. Here, we report the first series of HT-WM treated with chimeric antigen receptor T cells showing a high efficacy and no unexpected toxicity., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
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- 2024
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33. Brexucabtagene autoleucel in relapsed or refractory mantle cell lymphoma, intention-to-treat use in the DESCAR-T registry.
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Herbaux C, Bret C, Bachy E, Bories P, Di Blasi R, Cuffel A, Gastinne T, Lamy T, Roussel M, Bouabdallah K, Beauvais D, Cartron G, Bay JO, Blaise D, Rubio MT, Mohty M, Le Bras F, Casasnovas O, Guy J, Guidez S, Llorente CC, Hermine O, La Rochelle LD, Carras S, Guffroy B, Caillat-Zucman S, Houot R, and Le Gouill S
- Abstract
Not available.
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- 2024
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34. Dependence on mitochondrial respiration of malignant T cells reveals a new therapeutic target for angioimmunoblastic T-cell lymphoma.
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Krug A, Mhaidly R, Tosolini M, Mondragon L, Tari G, Turtos AM, Paul-Bellon R, Asnafi V, Marchetti S, Di Mascio L, Travert M, Bost F, Bachy E, Argüello RJ, Fournié JJ, Gaulard P, Lemonnier F, Ricci JE, and Verhoeyen E
- Abstract
Cancer metabolic reprogramming has been recognized as one of the cancer hallmarks that promote cell proliferation, survival, as well as therapeutic resistance. Up-to-date regulation of metabolism in T-cell lymphoma is poorly understood. In particular, for human angioimmunoblastic T-cell lymphoma (AITL) the metabolic profile is not known. Metabolic intervention could help identify new treatment options for this cancer with very poor outcomes and no effective medication. Transcriptomic analysis of AITL tumor cells, identified that these cells use preferentially mitochondrial metabolism. By using our preclinical AITL mouse model, mimicking closely human AITL features, we confirmed that T follicular helper (Tfh) tumor cells exhibit a strong enrichment of mitochondrial metabolic signatures. Consistent with these results, disruption of mitochondrial metabolism using metformin or a mitochondrial complex I inhibitor such as IACS improved the survival of AITL lymphoma-bearing mice. Additionally, we confirmed a selective elimination of the malignant human AITL T cells in patient biopsies upon mitochondrial respiration inhibition. Moreover, we confirmed that diabetic patients suffering from T-cell lymphoma, treated with metformin survived longer as compared to patients receiving alternative treatments. Taking together, our findings suggest that targeting the mitochondrial metabolic pathway could be a clinically efficient approach to inhibit aggressive cancers such as peripheral T-cell lymphoma., (© 2024. The Author(s).)
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- 2024
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35. Oral azacitidine compared with standard therapy in patients with relapsed or refractory follicular helper T-cell lymphoma (ORACLE): an open-label randomised, phase 3 study.
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Dupuis J, Bachy E, Morschhauser F, Cartron G, Fukuhara N, Daguindau N, Casasnovas RO, Snauwaert S, Gressin R, Fox CP, d'Amore FA, Staber PB, Tournilhac O, Bouabdallah K, Thieblemont C, André M, Rai S, Ennishi D, Gkasiamis A, Nishio M, Fornecker LM, Delfau-Larue MH, Sako N, Mule S, de Leval L, Gaulard P, Tsukasaki K, and Lemonnier F
- Subjects
- Humans, Male, Female, Aged, Middle Aged, Administration, Oral, Bendamustine Hydrochloride therapeutic use, Bendamustine Hydrochloride administration & dosage, Bendamustine Hydrochloride adverse effects, Gemcitabine, Lymphoma, Follicular drug therapy, Lymphoma, Follicular mortality, Deoxycytidine analogs & derivatives, Deoxycytidine therapeutic use, Deoxycytidine administration & dosage, Deoxycytidine adverse effects, Depsipeptides therapeutic use, Depsipeptides adverse effects, Depsipeptides administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antimetabolites, Antineoplastic therapeutic use, Antimetabolites, Antineoplastic adverse effects, Antimetabolites, Antineoplastic administration & dosage, Aged, 80 and over, Azacitidine therapeutic use, Azacitidine adverse effects, Azacitidine administration & dosage
- Abstract
Background: Follicular helper T-cell lymphomas (TFHL) harbour frequent alterations in genes that regulate DNA methylation. Preliminary reports suggest that treatment with 5-azacitidine has clinical activity in patients with relapsed or refractory TFHL. We aimed to compare the oral form of azacitidine with investigator's choice standard therapy (ICT; ie, gemcitabine, bendamustine, or romidepsin) in patients with relapsed or refractory TFHL., Methods: Patients older than 18 years with relapsed or refractory TFHL (angioimmunoblastic T-cell lymphoma, follicular lymphoma, or nodal T-cell lymphoma with phenotype, ie, positive with two or more markers among CD10, BCL6, CXCL13, PD1, or ICOS) based on the 2017 WHO classification of haematological neoplasms, with an Eastern Cooperative Oncology Group performance status score of 0-3, were recruited in university hospitals from five European countries and from Japan. Patients were randomly assigned 1:1 to treatment with either azacitidine given at a dose of 300 mg once a day (200 mg in Japanese patients) for 14 days in a 28-day cycle or gemcitabine, bendamustine, or romidepsin according to the investigator's choice. Random assignment was stratified by the number of previous lines of therapy and by the presence of previous or concomitant myeloid malignancy. The primary endpoint was investigator-assessed progression-free survival, presented in the intention-to-treat population. This Article is the final analysis of this trial, registered at ClinicalTrials.gov (Europe NCT03593018 and Japan NCT03703375)., Findings: 86 patients (median age 69 years [IQR 62-76], 50 patients were male, 36 were female) were enrolled between Nov 9, 2018, to Feb 22, 2021; 42 in the azacitidine group and 44 in the ICT group. With a median follow-up of 27·4 months (IQR 20·2-32·9), the median progression-free survival was 5·6 months (95% CI 2·7 -8·1) in the azacitidine group versus 2·8 months (1·9-4·8) in the ICT group (hazard ratio of 0·63 (95% CI 0·38-1·07); 1-sided p=0·042). Grade 3-4 adverse events were reported in 32 (76%) of 42 patients in the azacitidine group versus 42 (98%) of 43 patients in the ICT group. The most adverse grade 3 or worse adverse events were haematological (28 [67%] of 42 patients vs 40 [93%] of 43 patients), infection (8 [19%] and 14 [33%]), and gastrointestinal (5 [12%] vs 1 [2%] for azacitidine and ICT, respectively). There were two treatment-related deaths in the azacitidine group (one endocarditis and one candidiasis) and three in the ICT group (one heart failure, one COVID-19, and one cause unknown)., Interpretation: Although the pre-specified primary outcome of the trial was not met, the favourable safety profile suggests that azacitidine could add to the treatment options in these difficult to treat diseases especially in combination with other drugs. Trials with combination are in preparation in a platform trial., Funding: Bristol-Myers Squibb., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests EB reports receiving research funding from Amgen and Bristol-Myers Squibb (BMS); honoraria from Kite, Gilead, Novartis, Roche, Incyte, Miltenyi Biotech, Takeda, and Sanofi; and participation on an advisory committee for Roche, Gilead, ADC Therapeutics, Takeda, Novartis, and Incyte. FM reports receiving consultancy fees from Roche, Gilead, and AbbVie and participation on advisory committees for Roche, Gilead, Novartis, BMS, AbbVie, Genmab, Miltenyi, Allogene Therapeutics, AstraZeneca, and Janssen. GC reports receiving honoraria from Gilead, Novartis, Mylteni, Sanofi, AbbVie, Takeda, Roche, Janssen, Roche, Celgene, Novartis and participation on advisory committees for MabQi, Ownards Therapeutics, AbbVie, Roche, and BMS. NF reports receiving consultancy fees from AstraZeneca, AbbVie, Eli Lilly, HUYA, and Novartis; research funding from Bayer, BMS, Chugai Pharma, Celgene, Genmab, and Incyte; honoraria from AstraZeneca, BMS, Chugai Pharma, Dainippon Sumitomo, Eisai, Janssen, Kyowa Kirin, Nippon Shinyaku, Novartis, Ono, Sanofi, Symbio, Takeda, and Celgene. R-OC reports receiving honoraria from Roche, Takeda, Merck, BMS, Gilead and Kite, AbbVie, ADC Therapeutics, and Incyte; research funding from Takeda and Gilead and Kite; honoraria from Roche, Takeda, Merck, BMS, Gilead and Kite, AbbVie, ADC Therapeutics, Incyte and AstraZeneca; and participation on advisory committees for Roche, Takeda, Merck, BMS, Gilead and Kite, ADC Therapeutics, Janssen, and Incyte. CPF reports receiving consultancy fees from AbbVie, AstraZeneca, Atarabio, Celgene and BMS, GenMab, Gilead and Kite, Incyte, Janssen, Morphosys, Ono Pharmaceutical, Roche, and Takeda; research funding from BeiGene; and speaker bureau fees from Celgene and BMS, Gilead and Kite, Incyte, Janssen, Roche, and Takeda; and travel support from Roche. FAd’A reports receiving research funding from Servier and Nordic Nanovector. PBS reports receiving consultancy fees from Amgen, Roche, Janssen, Gilead, Incyte, Morphosys, CTI Biopharma, BMS, Celegene, AbbVie, Takeda, BMS, Beigene, and Lilly; research funding from Roche; and honoraria from Amgen, Roche, Janssen, Gilead, Incyte, Morphosys, CTI Biopharma, BMS, Celegene, AbbVie, Takeda, BMS, Beigene, and Lilly. AG and MN are current employees and stock option holders at BMS. L-MF reports receiving honoraria from Roche, AbbVie, Janssen, and AstraZeneca. M-HD-L reports receiving research funding from Roche and Celgene; honoraria from Gilead and Amgen and travel support from Mundipharma. LdL reports receiving consultancy fees from Lunaphore Technologies and Bayer and honoraria from Novartis. PG reports receiving consultancy fees from Takeda; research funding from Takeda, Innate Pharma, Alderan, and Sanofi; and honoraria from Takeda Gilead. KT reports receiving consultancy fees from Ono Pharma, Meiji Seika Pharma, Yakuruto, Solasia Pharma, Meiji Seika Pharma, and HUYABIO; research funding from Kyowa-hakko and Kirin, Meiji Seika Pharma, BMS, Byer, Daiich-Sankyo, HUYABIO, and Regeneron Pharmaceuticals; and honoraria from Chugai Pharma, Eizai, and Meiji Seika Pharma. FL reports receiving honoraria from Kiowa, Miltenyi, and BMS; research funding from Roche and BMS; and travel support from Roche and Gilead. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)
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- 2024
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36. Deep phenotyping of nodal T-cell lymphomas reveals immune alterations and therapeutic targets.
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Stephan P, Perrot J, Voisin A, Barbery M, Andrieu T, Grimont M, Caramel J, Bardou M, Tondeur G, Missiaglia E, Gaulard P, Lemmonier F, De Leval L, Bachy E, Sujobert P, Genestier L, Traverse-Glehen A, and Grinberg-Bleyer Y
- Abstract
Whereas immunotherapies have revolutionized the treatment of different solid and hematological cancers, their efficacy in nodal peripheral T-cell lymphomas (PTCLs) is limited, due to a lack of understanding of the immune response they trigger. To fully characterize the immune tumor microenvironment (TME) of PTCLs, we performed spectral flow cytometry analyses on 11 angioimmunoblastic T-cell lymphomas (AITL), 7 PTCL, not otherwise specified (PTCL, NOS) lymph node samples, and 10 non-tumoral control samples. The PTCL TME contained a larger proportion of regulatory T cells and exhausted CD8+ T cells, with enriched expression of druggable immune checkpoints. Interestingly, CD39 expression was up-regulated at the surface of most immune cells, and a multi-immunofluorescence analyses on a retrospective cohort of 43 AITL patients demonstrated a significant association between high CD39 expression by T cells and poor patient prognosis. Together, our study unravels the complex TME of nodal PTCLs, identifies targetable immune checkpoints, and highlights CD39 as a novel prognostic factor.
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- 2024
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37. Romidepsin Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Versus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Previously Untreated Peripheral T-Cell Lymphoma: Final Analysis of the Ro-CHOP Trial.
- Author
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Camus V, Thieblemont C, Gaulard P, Cheminant M, Casasnovas RO, Ysebaert L, Damaj GL, Guidez S, Pica GM, Kim WS, Lim ST, Andre M, Gutiérrez N, Penarrubia MJ, Staber PB, Trotman J, Hüttmann A, Stefoni V, Tucci A, Fogarty P, Farhat H, Abraham J, Abarah W, Belmecheri F, Ribrag V, Delfau-Larue MH, Cottereau AS, Itti E, Li J, Delarue R, de Leval L, Morschhauser F, and Bachy E
- Subjects
- Humans, Middle Aged, Male, Female, Aged, Adult, Progression-Free Survival, Lymphoma, T-Cell, Peripheral drug therapy, Lymphoma, T-Cell, Peripheral mortality, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cyclophosphamide administration & dosage, Cyclophosphamide therapeutic use, Doxorubicin administration & dosage, Doxorubicin therapeutic use, Vincristine administration & dosage, Vincristine therapeutic use, Prednisone administration & dosage, Prednisone therapeutic use, Depsipeptides administration & dosage, Depsipeptides therapeutic use
- Abstract
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The primary analysis of the Ro-CHOP phase III randomized controlled trial (ClinicalTrials.gov identifier: NCT01796002) established that romidepsin (Ro) plus cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) did not yield an increased efficacy compared with CHOP alone as first-line treatment of peripheral T-cell lymphoma. We report the planned final analysis 5 years after the last patient enrolled. With a median follow-up of 6 years, median progression-free survival (PFS) was 12.0 months compared with 10.2 months (hazard ratio [HR], 0.79 [95% CI, 0.62 to 1.005]; P = .054), while median overall survival was 62.2 months (35.7-86.6 months) and 43.8 months (30.1-70.2 months; HR, 0.88 [95% CI, 0.68 to 1.14]; P = .324) in the Ro-CHOP and CHOP arms, respectively. In an exploratory analysis, the median PFS in the centrally reviewed follicular helper T-cell lymphoma subgroup was significantly longer in the Ro-CHOP arm (19.5 v 10.6 months, HR, 0.703 [95% CI, 0.502 to 0.985]; P = .039). Second-line treatments were given to 251 patients with a median PFS2 and OS2 after relapse or progression of 3.3 months and 11.5 months, respectively. Within the limits of highly heterogeneous second-line treatments, no specific regimen seemed to provide superior disease control. However, a potential benefit was observed with brentuximab vedotin in association with chemotherapy even after excluding anaplastic large-cell lymphoma subtype or after adjusting for histology and international prognostic index in a multivariate model (HR for PFS, 0.431 [95% CI, 0.238 to 0.779]; P = .005).
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- 2024
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38. Durable response after tisagenlecleucel in adults with relapsed/refractory follicular lymphoma: ELARA trial update.
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Dreyling M, Fowler NH, Dickinson M, Martinez-Lopez J, Kolstad A, Butler J, Ghosh M, Popplewell L, Chavez JC, Bachy E, Kato K, Harigae H, Kersten MJ, Andreadis C, Riedell PA, Ho PJ, Pérez-Simón JA, Chen AI, Nastoupil LJ, von Tresckow B, María Ferreri AJ, Teshima T, Patten PEM, McGuirk JP, Petzer AL, Offner F, Viardot A, Zinzani PL, Malladi R, Paule I, Zia A, Awasthi R, Han X, Germano D, O'Donovan D, Ramos R, Maier HJ, Masood A, Thieblemont C, and Schuster SJ
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- Humans, Middle Aged, Male, Female, Aged, Adult, Immunotherapy, Adoptive adverse effects, Immunotherapy, Adoptive methods, Neoplasm Recurrence, Local drug therapy, Receptors, Antigen, T-Cell therapeutic use, Follow-Up Studies, Treatment Outcome, Lymphoma, Follicular drug therapy, Lymphoma, Follicular mortality
- Abstract
Abstract: Tisagenlecleucel is approved for adults with relapsed/refractory (r/r) follicular lymphoma (FL) in the third- or later-line setting. The primary analysis (median follow-up, 17 months) of the phase 2 ELARA trial reported high response rates and excellent safety profile in patients with extensively pretreated r/r FL. Here, we report longer-term efficacy, safety, pharmacokinetic, and exploratory biomarker analyses after median follow-up of 29 months (interquartile range, 22.2-37.7). As of 29 March 2022, 97 patients with r/r FL (grades 1-3A) received tisagenlecleucel infusion (0.6 × 108-6 × 108 chimeric antigen receptor-positive viable T cells). Bridging chemotherapy was allowed. Baseline clinical factors, tumor microenvironment, blood soluble factors, and circulating blood cells were correlated with clinical response. Cellular kinetics were assessed by quantitative polymerase chain reaction. Median progression-free survival (PFS), duration of response (DOR), and overall survival (OS) were not reached. Estimated 24-month PFS, DOR, and OS rates in all patients were 57.4% (95% confidence interval [CI], 46.2-67), 66.4% (95% CI, 54.3-76), and 87.7% (95% CI, 78.3-93.2), respectively. Complete response rate and overall response rate were 68.1% (95% CI, 57.7-77.3) and 86.2% (95% CI, 77.5-92.4), respectively. No new safety signals or treatment-related deaths were reported. Low levels of tumor-infiltrating LAG3+CD3+ exhausted T cells and higher baseline levels of naïve CD8+ T cells were associated with improved outcomes. Tisagenlecleucel continued to demonstrate highly durable efficacy and a favorable safety profile in this extended follow-up of 29 months in patients with r/r FL enrolled in ELARA. This trial was registered at www.clinicaltrials.gov as #NCT03568461., (© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2024
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39. Applying the EHA/EBMT grading for ICAHT after CAR-T: comparative incidence and association with infections and mortality.
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Rejeski K, Wang Y, Hansen DK, Iacoboni G, Bachy E, Bansal R, Penack O, Müller F, Bethge W, Munoz J, Mohty R, Bücklein VL, Barba P, Locke FL, Lin Y, Jain MD, and Subklewe M
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- Humans, Adult, Incidence, Adaptor Proteins, Signal Transducing, Receptors, Chimeric Antigen, Cytopenia, Neutropenia, Lymphoma, Mantle-Cell, Multiple Myeloma therapy
- Abstract
Abstract: Cytopenias represent the most common side effect of CAR T-cell therapy (CAR-T) and can predispose for severe infectious complications. Current grading systems, such as the Common Terminology Criteria for Adverse Events (CTCAE), neither reflect the unique quality of post-CAR-T neutrophil recovery, nor do they reflect the inherent risk of infections due to protracted neutropenia. For this reason, a novel EHA/EBMT consensus grading was recently developed for Immune Effector Cell-Associated HematoToxicity (ICAHT). In this multicenter, observational study, we applied the grading system to a large real-world cohort of 549 patients treated with BCMA- or CD19-directed CAR-T for refractory B-cell malignancies (112 multiple myeloma [MM], 334 large B-cell lymphoma [LBCL], 103 mantle cell lymphoma [MCL]) and examined the clinical sequelae of severe (≥3°) ICAHT. The ICAHT grading was strongly associated with the cumulative duration of severe neutropenia (r = 0.92, P < .0001), the presence of multilineage cytopenias, and the use of platelet and red blood cell transfusions. We noted an increased rate of severe ICAHT in patients with MCL vs those with LBCL and MM (28% vs 23% vs 15%). Severe ICAHT was associated with a higher rate of severe infections (49% vs 13%, P < .0001), increased nonrelapse mortality (14% vs 4%, P < .0001), and inferior survival outcomes (1-year progression-free survival: 35% vs 51%, 1-year overall survival: 52% vs 73%, both P < .0001). Importantly, the ICAHT grading demonstrated superior capacity to predict severe infections compared with the CTCAE grading (c-index 0.73 vs 0.55, P < .0001 vs nonsignificant). Taken together, these data highlight the clinical relevance of the novel grading system and support the reporting of ICAHT severity in clinical trials evaluating CAR-T therapies., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2024
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40. Transfusion needs after CAR T-cell therapy for large B-cell lymphoma: predictive factors and outcome (a DESCAR-T study).
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Vic S, Thibert JB, Bachy E, Cartron G, Gastinne T, Morschhauser F, Le Bras F, Bouabdallah K, Despas F, Bay JO, Rubio MT, Mohty M, Casasnovas O, Choquet S, Castilla-Llorente C, Guidez S, Loschi M, Guffroy B, Carras S, Drieu La Rochelle L, Guillet M, and Houot R
- Subjects
- Humans, Middle Aged, Quality of Life, Neoplasm Recurrence, Local, Biomarkers, Antigens, CD19, Immunotherapy, Adoptive adverse effects, Lymphoma, Large B-Cell, Diffuse pathology
- Abstract
Abstract: Chimeric antigen receptor (CAR) T-cells targeting CD19 have been approved for the treatment of relapse/refractory large B-cell lymphoma. Hematotoxicity is the most frequent CAR T-cell-related adverse event. Transfusion support is a surrogate marker of severe cytopenias. Transfusion affects patients' quality of life, presents specific toxicities, and is known to affect immunity through the so-called transfusion-related immunomodulation that may affect CAR T-cell efficacy. We analyzed data from 671 patients from the French DESCAR-T registry for whom exhaustive transfusion data were available. Overall, 401 (59.8%) and 378 (56.3%) patients received transfusion in the 6-month period before and after CAR T-cell infusion, respectively. The number of patients receiving transfusion and the mean number of transfused products increased during the 6-month period before CAR T-cell infusion, peaked during the first month after infusion (early phase), and decreased over time. Predictive factors for transfusion at the early phase were age >60 years, ECOG PS ≥2, treatment with axicabtagene ciloleucel, pre-CAR T-cell transfusions, and CAR-HEMATOTOX score ≥2. Predictive factors for late transfusion (between 1 and 6 months after infusion) were pre-CAR T-cell transfusions, CAR-HEMATOTOX score ≥2, ICANS ≥3 (for red blood cells [RBC] transfusion), and tocilizumab use (for platelets transfusion). Early transfusions and late platelets (but not RBC) transfusions were associated with a shorter progression-free survival and overall survival. Lymphoma-related mortality and nonrelapse mortality were both increased in the transfused population. Our data shed light on the mechanisms of early and late cytopenia and on the potential impact of transfusions on CAR T-cell efficacy and toxicity., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2024
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41. Three-year follow-up analysis of axicabtagene ciloleucel in relapsed/refractory indolent non-Hodgkin lymphoma (ZUMA-5).
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Neelapu SS, Chavez JC, Sehgal AR, Epperla N, Ulrickson M, Bachy E, Munshi PN, Casulo C, Maloney DG, de Vos S, Reshef R, Leslie LA, Oluwole OO, Yakoub-Agha I, Khanal R, Rosenblatt J, Korn R, Peng W, Lui C, Wulff J, Shen R, Poddar S, Jung AS, Miao H, Beygi S, and Jacobson CA
- Subjects
- Humans, Follow-Up Studies, Neoplasm Recurrence, Local drug therapy, Immunotherapy, Adoptive adverse effects, Antigens, CD19 therapeutic use, Biological Products therapeutic use, Lymphoma, Follicular drug therapy, Lymphoma, B-Cell, Marginal Zone drug therapy, Lymphoma, Large B-Cell, Diffuse pathology
- Abstract
Abstract: Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) follicular lymphoma (FL). Approval was supported by the phase 2, multicenter, single-arm ZUMA-5 study of axi-cel for patients with R/R indolent non-Hodgkin lymphoma (iNHL; N = 104), including FL and marginal zone lymphoma (MZL). In the primary analysis (median follow-up, 17.5 months), the overall response rate (ORR) was 92% (complete response rate, 74%). Here, we report long-term outcomes from ZUMA-5. Eligible patients with R/R iNHL after ≥2 lines of therapy underwent leukapheresis, followed by lymphodepleting chemotherapy and axi-cel infusion (2 × 106 CAR T cells per kg). The primary end point was ORR, assessed in this analysis by investigators in all enrolled patients (intent-to-treat). After median follow-up of 41.7 months in FL (n = 127) and 31.8 months in MZL (n = 31), ORR was comparable with that of the primary analysis (FL, 94%; MZL, 77%). Median progression-free survival was 40.2 months in FL and not reached in MZL. Medians of overall survival were not reached in either disease type. Grade ≥3 adverse events of interest that occurred after the prior analyses were largely in recently treated patients. Clinical and pharmacokinetic outcomes correlated negatively with recent exposure to bendamustine and high metabolic tumor volume. After 3 years of follow-up in ZUMA-5, axi-cel demonstrated continued durable responses, with very few relapses beyond 2 years, and manageable safety in patients with R/R iNHL. The ZUMA-5 study was registered at www.clinicaltrials.gov as #NCT03105336., (© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2024
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42. Retrospective multicenter comparative study of the efficacy and safety between R-DHAC and R-DHAOx in diffuse large B-cell lymphoma or transformed follicular or marginal zone B lymphoma into aggressive lymphoma, as a second-line treatment.
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Fouillet L, Daguenet E, Tavernier E, Ghesquières H, Bachy E, Sesques P, Tournilhac O, Bay JO, Michallet AS, Sapet M, Chalayer E, Guyotat D, Tinquaut F, and Cornillon J
- Subjects
- Humans, Retrospective Studies, Lymphoma, B-Cell, Marginal Zone pathology, Lymphoma, Follicular pathology, Lymphoma, Large B-Cell, Diffuse pathology
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- 2024
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43. Functional precision oncology for follicular lymphoma with patient-derived xenograft in avian embryos.
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Zala M, Lipinski B, Costechareyre C, Jarrosson L, Teinturier R, Julia E, Lacourrège M, Verney A, Guitton J, Traverse-Glehen A, Bachy E, Salles G, Huet S, Genestier L, Castellani V, Delloye-Bourgeois C, and Sujobert P
- Subjects
- Humans, Heterografts, Precision Medicine, Medical Oncology, Lymphoma, Follicular genetics, Lymphoma, Follicular pathology
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- 2024
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44. Metabolic tumor volume predicts outcome in patients with advanced stage follicular lymphoma from the RELEVANCE trial.
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Cottereau AS, Rebaud L, Trotman J, Feugier P, Nastoupil LJ, Bachy E, Flinn IW, Haioun C, Ysebaert L, Bartlett NL, Tilly H, Casasnovas O, Ricci R, Portugues C, Buvat I, Meignan M, and Morschhauser F
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- Humans, Tumor Burden, Prognosis, Progression-Free Survival, Positron-Emission Tomography, Fluorodeoxyglucose F18, Retrospective Studies, Positron Emission Tomography Computed Tomography methods, Lymphoma, Follicular diagnostic imaging, Lymphoma, Follicular drug therapy
- Abstract
Background: We investigated the prognostic value of baseline positron emission tomography (PET) parameters for patients with treatment-naïve follicular lymphoma (FL) in the phase III RELEVANCE trial, comparing the immunomodulatory combination of lenalidomide and rituximab (R
2 ) versus R-chemotherapy (R-chemo), with both regimens followed by R maintenance therapy., Patients and Methods: Baseline characteristics of the entire PET-evaluable population (n = 406/1032) were well balanced between treatment arms. The maximal standard uptake value (SUVmax ) and the standardized maximal distance between tow lesions (SDmax ) were extracted, the standardized distance between two lesions the furthest apart, were extracted. The total metabolic tumor volume (TMTV) was computed using the 41% SUVmax method., Results: With a median follow-up of 6.5 years, the 6-year progression-free survival (PFS) was 57.8%, the median TMTV was 284 cm3 , SUVmax was 11.3 and SDmax was 0.32 m-1 , with no significant difference between arms. High TMTV (>510 cm3 ) and FLIPI were associated with an inferior PFS (P = 0.013 and P = 0.006, respectively), whereas SUVmax and SDmax were not (P = 0.08 and P = 0.12, respectively). In multivariable analysis, follicular lymphoma international prognostic index (FLIPI) and TMTV remained significantly associated with PFS (P = 0.0119 and P = 0.0379, respectively). These two adverse factors combined stratified the overall population into three risk groups: patients with no risk factors (40%), with one factor (44%), or with both (16%), with a 6-year PFS of 67.7%, 54.5%, and 41.0%, respectively. No significant interaction between treatment arms and TMTV or FLIPI (P = 0.31 or P = 0.59, respectively) was observed. The high-risk group (high TMTV and FLIPI 3-5) had a similar PFS in both arms (P = 0.45) with a median PFS of 68.4% in the R-chemo arm versus 71.4% in the R2 arm., Conclusions: Baseline TMTV is predictive of PFS, independently of FLIPI, in patients with advanced FL even in the context of antibody maintenance., (Copyright © 2023 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)- Published
- 2024
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45. Outcome and factors associated with mortality in patients receiving urgent chemotherapy in the ICU: A retrospective study.
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Bernard J, Vacheron CH, Vantard N, Bachy E, Richard JC, Aubrun F, Cour M, Lukaszewicz AC, Bohe J, Allaouchiche B, Friggeri A, and Wallet F
- Subjects
- Adult, Humans, Retrospective Studies, Prognosis, Intensive Care Units, Hospital Mortality, Hematologic Neoplasms, Leukemia, Myeloid, Acute
- Abstract
Purpose: This study aimed to assess the outcome and factors associated with mortality in patients who received urgent chemotherapy (CT) in the intensive care unit (ICU) in Lyon, France., Material and Methods: A total of 147 adult patients diagnosed with cancer and requiring urgent CT during ICU stay between October 2014 and December 2019 were included in this retrospective study., Results: Hematological cancer was found in 77% of patients, and acute respiratory failure was the leading cause of ICU admission (46.3%). The 6-month mortality rate was 69.4%; patients with solid cancer had a higher risk of mortality. Patients who died within 6 months had a poor performance score and a higher SOFA score at admission. The multivariate analysis showed that solid tumors, sepsis on the day of CT, and SOFA score on the day of CT were associated with 6-month mortality. Additionally, 95% of patients who survived the ICU resumed conventional CT, with a higher likelihood of resuming CT among those with hematological cancer., Conclusion: Urgent CT in the ICU is feasible in a specific subset of patients, mainly those with hematological cancer, with resumption of the curative treatment regimen after ICU discharge., Competing Interests: Declaration of Competing Interest J. BERNARD has no conflict of interest. C.H. VACHERON has no conflict of interest. N. VANTARD has no conflict of interest. E. BACHY has no conflict of interest. J.C. RICHARD has no conflict of interest. F. AUBRUN has no conflict of interest. M. COUR has no conflict of interest. AC. LUKASZEWICZ has no conflict of interest. J. BOHE has no conflict of interest. B. ALLAOUCHICHE has no conflict of interest. A. FRIGGERI has no conflict of interest. F. WALLET has no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
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46. Nonrelapse mortality after CAR T-cell therapy for large B-cell lymphoma: a LYSA study from the DESCAR-T registry.
- Author
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Lemoine J, Bachy E, Cartron G, Beauvais D, Gastinne T, Di Blasi R, Rubio MT, Guidez S, Mohty M, Casasnovas RO, Joris M, Castilla-Llorente C, Haioun C, Hermine O, Loschi M, Carras S, Bories P, Fradon T, Herbaux C, Sesques P, Le Gouill S, Morschhauser F, Thieblemont C, and Houot R
- Subjects
- Humans, Risk Factors, Antigens, CD19, Immunotherapy, Adoptive adverse effects, Immunotherapy, Adoptive methods, Lymphoma, Large B-Cell, Diffuse pathology
- Abstract
CD19 chimeric antigen receptor (CAR) T cells can induce prolonged remissions and potentially cure a significant proportion of patients with relapsed/refractory large B-cell lymphomas. However, some patients may die of causes unrelated to lymphoma after CAR T-cell therapy. To date, little is known about the nonrelapse mortality (NRM) after CAR T-cell therapy. Using the French DESCAR-T registry, we analyzed the incidence and causes of NRM and identified risk factors of NRM. We report on 957 patients who received standard-of-care axicabtagene ciloleucel (n = 598) or tisagenlecleucel (n = 359) between July 2018 and April 2022, in 27 French centers. With a median follow-up of 12.4 months, overall NRM occurred in 48 patients (5.0% of all patients): early (before day 28 after infusion) in 9 patients (0.9% of all patients and 19% of overall NRM), and late (on/after day 28 after infusion) in 39 patients (4.1% of all patients and 81% of overall NRM). Causes of overall NRM were distributed as follows: 56% infections (29% with non-COVID-19 and 27% with COVID-19), 10% cytokine release syndromes, 6% stroke, 6% cerebral hemorrhage, 6% second malignancies, 4% immune effector cell associated neurotoxicities, and 10% deaths from other causes. We report risk factors of early NRM and overall NRM. In multivariate analysis, both diabetes and elevated ferritin level at lymphodepletion were associated with an increased risk of overall NRM. Our results may help physicians in patient selection and management in order to reduce the NRM after CAR T-cell therapy., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2023
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47. The CAR-HEMATOTOX score identifies patients at high risk for hematological toxicity, infectious complications, and poor treatment outcomes following brexucabtagene autoleucel for relapsed or refractory MCL.
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Rejeski K, Wang Y, Albanyan O, Munoz J, Sesques P, Iacoboni G, Lopez-Corral L, Ries I, Bücklein VL, Mohty R, Dreyling M, Baluch A, Shah B, Locke FL, Hess G, Barba P, Bachy E, Lin Y, Subklewe M, and Jain MD
- Subjects
- Humans, Adult, Treatment Outcome, Immunotherapy, Adoptive, Progression-Free Survival, Lymphoma, Mantle-Cell drug therapy, Neutropenia
- Abstract
CD19-directed CAR T-cell therapy with brexucabtagene autoleucel (brexu-cel) has substantially improved treatment outcomes for patients with relapsed/refractory mantle cell lymphoma (r/r MCL). Prolonged cytopenias and infections represent common and clinically relevant side effects. In this multicenter observational study, we describe cytopenias and infections in 103 r/r MCL patients receiving brexu-cel. Furthermore, we report associations between the baseline CAR-HEMATOTOX (HT) score and toxicity events, non-relapse mortality (NRM), and progression-free/overall survival (PFS/OS). At lymphodepletion, 56 patients were HT
low (score 0-1) while 47 patients were HThigh (score ≥2). The HThigh cohort exhibited prolonged neutropenia (median 14 vs. 6 days, p < .001) and an increased rate of severe infections (30% vs. 5%, p = .001). Overall, 1-year NRM was 10.4%, primarily attributed to infections, and differed by baseline HT score (high vs. low: 17% vs. 4.6%, p = .04). HThigh patients experienced inferior 90-day complete response rate (68% vs. 93%, p = .002), PFS (median 9 months vs. not-reached, p < .0001), and OS (median 26 months vs. not-reached, p < .0001). Multivariable analyses showed that high HT scores were independently associated with severe hematotoxicity, infections, and poor PFS/OS. In conclusion, infections and hematotoxicity are common after brexu-cel and contribute to NRM. The baseline HT score identified patients at increased risk of poor treatment outcomes., (© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)- Published
- 2023
- Full Text
- View/download PDF
48. Molecular Characterization of Primary Mediastinal Large B-Cell Lymphomas.
- Author
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Donzel M, Pesce F, Trecourt A, Groussel R, Bachy E, Ghesquières H, Fontaine J, Benzerdjeb N, Mauduit C, and Traverse-Glehen A
- Abstract
Since the description of primary mediastinal large B-cell lymphoma (PMBL) as a distinct entity from diffuse large B-cell lymphomas (DLBCL), numerous studies have made it possible to improve their definition. Despite this, this differential diagnosis can be challenging in daily practice. However, in some centers, PMBL may be treated according to a particular regimen, distinct from those used in DLBCL, emphasizing the importance of accurate identification at diagnosis. This study aimed to describe the histological and molecular characteristics of PMBL to improve the accuracy of their diagnosis. Forty-nine cases of PMBL were retrospectively retrieved. The mean age at diagnosis was 39 years (21-83), with a sex ratio of 0.88. All cases presented a fibrous background with diffuse growth of intermediate to large cells with an eosinophil (26/49, 53%) or retracted cytoplasm (23/49, 47%). "Hodgkin-like" cells were observed in 65% of cases (32/49, 65%). The phenotype was: BCL6+ (47/49, 96%), MUM1+ (40/49, 82%), CD30+ (43/49, 88%), and CD23+ (37/49, 75%). Genomic DNAs were tested by next generation sequencing of 33 cases using a custom design panel. Pathogenic variants were found in all cases. The most frequent mutations were: SOCS1 (30/33, 91%), TNFAIP3 (18/33, 54.5%), ITPKB (17/33, 51.5%), GNA13 (16/33, 48.5%), CD58 (12/33, 36.4%), B2M (12/33; 36.4%), STAT6 (11/33, 33.3%) as well as ARID1A (10/33, 30.3%), XPO1 (9/33, 27.3%), CIITA (8/33, 24%), and NFKBIE (8/33, 24%). The present study describes a PMBL cohort on morphological, immunohistochemical, and molecular levels to provide pathologists with daily routine tools. These data also reinforce interest in an integrated histomolecular diagnosis to allow a precision diagnosis as early as possible.
- Published
- 2023
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49. Publisher Correction: Axicabtagene ciloleucel as second-line therapy in large B cell lymphoma ineligible for autologous stem cell transplantation: a phase 2 trial.
- Author
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Houot R, Bachy E, Cartron G, Gros FX, Morschhauser F, Oberic L, Gastinne T, Feugier P, Duléry R, Thieblemont C, Joris M, Jardin F, Choquet S, Casasnovas O, Brisou G, Cheminant M, Bay JO, Gutierrez FL, Menard C, Tarte K, Delfau MH, Portugues C, Itti E, Palard-Novello X, Blanc-Durand P, Al Tabaa Y, Bailly C, Laurent C, and Lemonnier F
- Published
- 2023
- Full Text
- View/download PDF
50. Post-transplantation Burkitt lymphoma: a retrospective study of 55 patients.
- Author
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Walczak P, Choquet S, Dantal J, Boutboul D, Suarez F, Baron M, Morel V, Cluzeau T, Touati M, Elias M, Bachy E, Nicolas-Virelizier E, Houot R, Venton G, Jacquet C, Moles-Moreau MP, Jardin F, Durot E, Balegroune N, Ecotiere L, Guieze R, Kamar N, Ysebaert L, Couzi L, Gonzalez H, Roulin L, Ou K, Caillard S, Zimmermann H, Trappe RU, and Roos-Weil D
- Subjects
- Humans, Retrospective Studies, Cyclophosphamide therapeutic use, Antineoplastic Combined Chemotherapy Protocols, Burkitt Lymphoma genetics, Burkitt Lymphoma drug therapy
- Published
- 2023
- Full Text
- View/download PDF
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