Clinical and Product Features Associated with Outcome of DLBCL Patients to CD19-Targeted CAR T-Cell Therapy
Sylvain Lamure, François Van Laethem, Delphine de Verbizier, Claire Lozano, Eve Gehlkopf, Jean‐Jacques Tudesq, Chris Serrand, Mehdi Benzaoui, Tarik Kanouni, Adeline Quintard, John De Vos, Emmanuelle Tchernonog, Laura Platon, Xavier Ayrignac, Patrice Céballos, Anne Sîrvent, Mickael François, Hanane Guedon, Philippe Quittet, Cédric Mongellaz, Aurélie Conte, Charles Herbaux, Caroline Bret, Naomi Taylor, Valérie Dardalhon, Guillaume Cartron
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.