Abstract
Both anti-CD19 chimeric antigen receptor (CAR)-T cell therapy and CD20xCD3 bispecific antibodies (BsAbs) are recommended as preferred regimens of third-line and subsequent treatment for follicular lymphoma (FL). We aimed to compare the efficacy and safety of CAR-T and BsAbs in third- or later-line treatments for relapsed or refractory (R/R) FL. We reviewed trials from PubMed, Embase and Cochrane Library databases up to January 31, 2025. Primary endpoint was overall response rate (ORR). Secondary endpoints included complete response rate (CRR), 12-month progression-free survival (PFS), and grade ≥ 3 adverse events of cytokine release syndrome (CRS), neurotoxicity, and infection. Eight studies comprising 725 grade 1-3a FL patients with R/R disease after ≥ 2 lines of systemic therapy were included in the meta-analysis. The pooled ORR was 0.93 (95% CI, 0.84–0.97) for CAR-T and 0.81 (95% CI, 0.77–0.85) for BsAbs (P = 0.02). For safety profiles, no significant difference was observed between the two groups in terms of grade ≥ 3 CRS, neurotoxicity, and infections. Anti-CD19 CAR-T cell therapy exhibited higher ORR compared to CD20xCD3 BsAbs as third- or later-line treatment for R/R FL with comparable toxicities. Registration: PROSPERO 2025 CRD420251005804.