Comparative real-world outcomes of CD19-directed CAR T-cell therapies in large B-cell lymphoma

Although 3 commercial CD19-targeted chimeric antigen receptor (CAR) T-cell therapies are available for large B-cell lymphomas (LBCLs), no randomized clinical trials have compared their efficacy and safety. In this retrospective multicenter cohort study, we evaluated real-world clinical outcomes of patients with relapsed/refractory LBCL treated with axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), or lisocabtagene maraleucel (liso-cel). Between April 2016 and July 2024, 624 patients received CD19-targeted CAR T-cell therapies (344 axi-cel, 142 tisa-cel, and 138 liso-cel). At a median follow-up of 20.9 months, the respective estimated 2-year progression-free survival (PFS) and overall survival (OS) rates were 46% and 63% for axi-cel, 30% and 45% for tisa-cel, and 45% and 58% for liso-cel. After adjusting for potential confounders in multivariate analyses, tisa-cel was associated with inferior PFS and OS compared to axi-cel. No significant survival differences were found between liso-cel and axi-cel. Propensity score and subanalyses of patients treated in the second-line vs third-line or later settings yielded similar outcomes. Compared to axi-cel, the objective response rate at 100 days was higher for liso-cel and lower for tisa-cel. Rates of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and immune effector cell-associated hematotoxicity, and febrile neutropenia were significantly higher with axi-cel. However, no significant differences in the cumulative incidence of infections or nonrelapse mortality were found. Axi-cel was associated with faster vein-to-vein time (axi-cel, 35 days; tisa-cel, 43 days; liso-cel, 41 days) and fewer out-of-specification products (axi-cel, 2%; tisa-cel, 4%; liso-cel, 11%). These results provide insights into potential differential outcomes depending on product selection.