Indirect Treatment Comparisons of Lisocabtagene Maraleucel Versus Axicabtagene Ciloleucel and Tisagenlecleucel in Third-Line or Later Relapsed or Refractory Follicular Lymphoma

No head-to-head clinical trials have compared CD19-directed chimeric antigen receptor (CAR) T cell therapies for treatment of follicular lymphoma (FL). We conducted matching-adjusted indirect comparisons (MAICs) between lisocabtagene maraleucel (liso-cel), axicabtagene ciloleucel (axi-cel), and tisagenlecleucel (tisa-cel), to establish their relative efficacy and safety in patients with third-line or later (3L+) relapsed or refractory (R/R) FL. Sources included individual patient data from TRANSCEND FL (NCT04245839) for liso-cel, summary-level data from ZUMA-5 (NCT03105336) for axi-cel, and summary-level data from ELARA (NCT03568461) for tisa-cel. For each MAIC, TRANSCEND FL patients who met inclusion/exclusion criteria for the comparator study were included. MAICs adjusted for clinically relevant prognostic factors identified a priori to minimize population differences between studies. After adjustment, liso-cel had a higher complete response (CR) rate than axi-cel (response ratio RR 1.24, 95% confidence interval CI 1.07‒1.43) and tisa-cel (RR 1.36, 95% CI 1.11‒1.68) and a higher overall response rate (ORR) than tisa-cel (RR 1.12, 95% CI 1.01‒1.24). Estimates numerically favored liso-cel for progression-free survival, duration of response, overall survival, and time to next treatment, though were not statistically significant. Liso-cel demonstrated better safety than axi-cel, with significantly reduced odds ratios (ORs) of grade ≥ 3 cytokine release syndrome (CRS; OR 0.07, 95% CI 0.01‒0.58), tocilizumab use for CRS (OR 0.20, 95% CI 0.09‒0.44), any-grade neurological events (NEs; OR 0.14, 95% CI 0.05‒0.38), and infections (OR 0.42, 95% CI 0.19‒0.93). Liso-cel and tisa-cel had similar safety profiles overall, excluding any-grade NEs, which was significantly lower for liso-cel (OR 0.19, 95% CI 0.08‒0.45). After adjustment for population differences, liso-cel demonstrated a higher CR rate and numerically favorable trends of survival compared to axi-cel and tisa-cel with improved safety compared to axi-cel, and similar safety compared to tisa-cel. These findings underscore liso-cel as a potentially preferred CAR T cell therapy for 3L+ R/R FL. Graphical Abstract available for this article.