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

Although 3 commercial CD19-targeted CAR T-cell therapies are available for large B-cell lymphoma (LBCL), 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, estimated 2-year PFS and OS rates were 46%/63% for axi-cel, 30%/45% for tisa-cel, and 45%/58% for liso-cel. After adjusting for potential confounders in multivariable analyses, tisa-cel was associated with inferior progression-free survival (PFS) (hazard ratio [HR] = 2.25; 95% confidence interval [CI]: 1.65-3.06; p < 0.001) and overall survival (OS) (HR = 1.68; 95% CI: 1.19-2.36; p = 0.003) 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 (odds ratio [OR] = 2.31; 95% CI: 1.21-4.80; p = 0.016) and lower for tisa-cel (OR = 0.36; 95% CI: 0.23-0.57; p < 0.001). Rates of CRS, ICANS, ICAHT, and febrile neutropenia were significantly higher with axi-cel. However, no significant differences in the cumulative incidence of infections or non-relapse 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; p < 0.001) and fewer out-of-specification products (axi-cel: 2%, tisa-cel: 4%, liso-cel: 11%; p = 0.004). These results provide insights into potential differential outcomes depending on product selection.