Real-World Outcomes and Toxicities of CAR-T in Relapsed/Refractory Follicular Lymphoma: A Multicenter Cohort Study

Chimeric antigen receptor T-cell (CAR-T) therapy revolutionized treatment of relapsed/refractory (R/R) follicular lymphoma (FL). Real-world efficacy and toxicity data are needed as clinical trial populations are often not representative. Hence, we conducted a multi-center retrospective study of patients with R/R FL undergoing commercial CAR-T with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) between 2021 and 2024. Endpoints included measures of efficacy (overall response rate [ORR], complete response rate [CRR], progression-free survival [PFS], and overall survival [OS]) and toxicity (rates of cytokine release syndrome [CRS] and immune effector cell-associated neurotoxicity syndrome [ICANS]). Among 136 patients, 100 (74%) received axi-cel and 36 (26%) received tisa-cel. Axi-cel patients were younger (median age 60 vs 68 years, p=0.001) and received bendamustine lymphodepletion less often (9% vs 33%, p<0.001). Median follow up was 14.4 months (range 0.8 - 72.0 months). In the unweighted analysis, axi-cel was associated with higher ORR (96% vs 80%, p=0.007), CRR (88% vs 71%, p=0.024), and longer median PFS (30.5 months vs 11.9 months, p=0.021) compared with tisa-cel. Median OS did not differ significantly between the two products (not reached vs 23.6 months, p=0.061). Rates of CRS were comparable (75% vs 75%, p=0.99), whereas ICANS occurred more frequently with axi-cel (42% vs 17%, p=0.008). After inverse probability of treatment weighting, efficacy outcomes were largely similar between axi-cel and tisa-cel, however, axi-cel remained associated with significantly higher toxicity. In real-world settings, both axi-cel and tisa-cel demonstrated efficacy in patients with R/R FL, although PFS was inferior to that reported in clinical trials.