Sequencing antibody-based and CAR-T therapies in relapsed/refractory follicular lymphoma: An anchored indirect comparison and parallel meta-analysis.

Abstract

e19053 Background: Therapeutic options for relapsed/refractory (R/R) follicular lymphoma (FL) now include dual-targeted CD19/CD20 antibody regimens, CD20×CD3 bispecific antibodies, and chimeric antigen receptor (CAR) T-cell therapies. However, the relative efficacy of antibody-based platforms and their positioning relative to CAR-T remain unclear due to the absence of head-to-head trials. We performed an anchored indirect comparison to evaluate progression-free survival (PFS) between antibody-based regimens and conducted a parallel meta-analysis to contextualize CAR-T outcomes. Methods: A systematic review identified phase III randomized trials in R/R FL sharing a lenalidomide–rituximab (R²) backbone. An anchored Bucher indirect comparison was performed between tafasitamab plus R² and epcoritamab plus R² using reported PFS hazard ratios (HRs). CAR-T therapies, which lack randomized comparators, were analyzed separately using a random-effects meta-analysis of proportions to estimate pooled overall response rate (ORR) and complete response (CR) rates. Safety outcomes were compared descriptively across therapeutic classes. Results: Compared with R², tafasitamab plus R² improved PFS (HR 0.43, 95% CI 0.32–0.58), as did epcoritamab plus R² (HR 0.21, 95% CI 0.14–0.31). In the anchored indirect comparison, epcoritamab plus R² demonstrated superior PFS relative to tafasitamab plus R² (HR 0.49, 95% CI 0.30–0.80; p=0.0047). In a parallel meta-analysis of CAR-T therapies (ZUMA-5 and ELARA; n=178), pooled ORR was 90.2% (95% CI 83.0–94.6) with moderate heterogeneity (I²=65%), and pooled CR rate was 73.6% (95% CI 66.5–79.7). CAR-T therapies achieved the highest depth of response but were associated with higher rates of acute toxicity, including cytokine release syndrome and neurotoxicity. Bispecific antibody therapy demonstrated strong PFS benefit with outpatient administration but higher rates of serious infections, while dual-targeted antibody therapy showed intermediate efficacy with a potentially favorable tolerability profile. Conclusions: In an anchored indirect comparison, CD20×CD3 bispecific antibody therapy was associated with significantly improved PFS compared with dual-targeted CD19/CD20 antibody therapy in R/R FL. CAR-T therapies achieved the highest response rates in parallel analyses but with increased acute toxicity. These findings support a risk-adapted, sequential treatment approach in R/R follicular lymphoma.