Clinical and Product Features Associated with Outcome of DLBCL Patients to CD19-Targeted CAR T-Cell Therapy

SIMPLE SUMMARY: Factors impacting the response to CAR T-cell therapies are not fully understood. In this monocentric prospective study, we describe the outcome of 60 patients with relapsed/refractory diffuse large B-cell lymphoma and transformed follicular lymphoma infused with CD19-directed CAR T-cell products, axicabtagene ciloleucel and tisagenlecleucel. We obtained a 40% complete metabolic response and a 27% partial metabolic response with a median progression-free survival of 3.1 months and a median of overall survival of 12.3 months. We also found that age-adjusted IPI at the time of infusion, product features, in vivo expansion, and CAR T-cell exhaustion phenotype were significatively associated with the efficacy of the CAR T-cell therapy. 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.