Naïve CD4+ T-cells and disease status at CART infusion correlate with clinical outcomes in real-world large B-cell lymphoma patients receiving second-line CAR T therapy

Axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel) are standard-of-care second-line therapies for relapsed or refractory large B-cell lymphomas, yet clinical and immunological predictors of durable benefit remain poorly defined. Here, we retrospectively analyze 64 patients treated with second-line commercial axi-cel (n = 35) or liso-cel (n = 29). Overall (66%) and complete (55%) response rates are similar between CART products. The 24-month progression-free survival (PFS) and overall survival rates are 46% and 76%, respectively. Primary refractory disease and progressive disease at infusion are associated with inferior response rates on multivariate analysis. Importantly, toxicity rate is relatively low, with 3% of patients experiencing Grade 3-4 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Furthermore, lower CD4+ T-cell counts at apheresis correlate with inferior PFS. Immunophenotyping reveals that higher naïve CD4+ T-cell counts at apheresis predict durable response in axi-cel-treated patients. Greater CART expansion, enrichment for naïve CD8+ CAR+ T-cells, and lower PD1 expression at day 7 post-infusion are associated with response. Thus, these findings highlight the efficacy of second-line CART and identify disease and immune-related predictors of long-term response. Second-line CAR T cell therapies have become standard-of-care treatments for relapsed or refractory large B-cell lymphomas (LBCL). However, real-world evidence on the efficacy and immunological phenotypes is limited. Here, the authors present a retrospective single-center study of 64 patients treated with axi-cel or liso-cel and report efficacy and safety readouts. By performing immunophenotypic analysis on samples from apheresis and post CAR T cell infusion, the authors also investigate how the magnitude of CAR T expansion and early phenotypic features influence persistence and therapeutic outcomes.