1. Clinical and Product Features Associated with Outcome of DLBCL Patients to CD19-Targeted CAR T-Cell Therapy
- Author
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Anne Sirvent, Claire Lozano, Cédric Mongellaz, Guillaume Cartron, Hanane Guedon, François Van Laethem, Adeline Quintard, Mehdi Benzaoui, John De Vos, Aurélie Conte, Laura Platon, Jean-Jacques Tudesq, Delphine De Verbizier, Tarik Kanouni, Xavier Ayrignac, Patrice Ceballos, Chris Serrand, Mickael François, Emmanuelle Tchernonog, Eve Gehlkopf, Naomi Taylor, Valerie Dardalhon, Sylvain Lamure, Caroline Bret, Charles Herbaux, Philippe Quittet, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), CHU Montpellier, and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
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Oncology ,Cancer Research ,medicine.medical_specialty ,Follicular lymphoma ,diffuse large B-cell lymphoma ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,CAR T-cell ,CD19 ,Article ,03 medical and health sciences ,0302 clinical medicine ,International Prognostic Index ,immune-monitoring ,Refractory ,In vivo ,Internal medicine ,T-cell exhaustion ,medicine ,ComputingMilieux_MISCELLANEOUS ,tisagenleucleucel ,RC254-282 ,030304 developmental biology ,0303 health sciences ,biology ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,medicine.disease ,3. Good health ,Lymphoma ,axicabtagene ciloleucel ,030220 oncology & carcinogenesis ,biology.protein ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,standard-of-care ,business ,Diffuse large B-cell lymphoma ,CD8 - Abstract
CD19-directed CAR T-cells have been remarkably successful in treating patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and transformed follicular lymphoma (t-FL). In this cohort study, we treated 60 patients with axicabtagene ciloleucel or tisagenlecleucel. Complete and partial metabolic responses (CMR/PMR) were obtained in 40% and 23% of patients, respectively. After 6.9 months of median follow-up, median progression-free survival (mPFS) and overall survival (mOS) were estimated at 3.1 and 12.3 months, respectively. Statistical analyses revealed that CMR, PFS, and OS were all significantly associated with age-adjusted international prognostic index (aaIPI, p <, 0.05). T-cell subset phenotypes in the apheresis product tended to correlate with PFS. Within the final product, increased percentages of both CD4 and CD8 CAR+ effector memory cells (p = 0.02 and 0.01) were significantly associated with CMR. Furthermore, higher CMR/PMR rates were observed in patients with a higher maximal in vivo expansion of CAR T-cells (p = 0.05) and lower expression of the LAG3 and Tim3 markers of exhaustion phenotype (p = 0.01 and p = 0.04). Thus, we find that aaIPI at the time of infusion, phenotype of the CAR T product, in vivo CAR T-cell expansion, and low levels of LAG3/Tim3 are associated with the efficacy of CAR T-cell therapy in DLBCL patients.
- Published
- 2021
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