Meta-analysis of comparing CAR-T and bispecific antibody therapy in relapsed/refractory indolent B-cell non-Hodgkin's lymphomas.

[BACKGROUND] Indolent B-cell non-Hodgkin’s lymphomas (B-NHLs), including follicular lymphoma (FL) and marginal zone lymphoma (MZL), typically demonstrate slow progression but frequently follow a relapsing-remitting course with conventional therapies. Chimeric antigen receptor T-cell (CAR-T) and bi-specific antibodies (BsAbs) therapies have revolutionized treatment for relapsed/refractory (R/R) B-NHLs. However comparative data on the efficacy of CAR-T therapy versus BsAbs in indolent B-NHLs remain limited. This meta-analysis systematically evaluated the efficacy and safety profiles of these two innovative treatments in patients with R/R FL and MZL.

[METHODS] We conducted a comprehensive search of MEDLINE, Embase, Cochrane Central Register of Controlled Trial databases, and international conference abstracts (through June 30, 2025) for studies investigating CAR-T or BsAb therapies in R/R FL and MZL. Primary outcome was pooled complete response (CR) rate. Other outcomes included 2-year progression-free survival (PFS), 2-year overall survival (OS), non-relapse mortality (NRM), and adverse events (AEs). Meta-regression analyses were performed to adjust for relevant clinical covariates.

[RESULTS] Our analysis included 19 publications ( = 1,760 patients), comprising 10 CAR-T and 9 BsAbs studies. The single-arm meta-analysis showed that CAR-T therapy demonstrated superior efficacy, with higher pooled CR rate (80.73% vs. 67.14%;  = 0.0003), 2-year PFS (68.84% vs. 47.71%;  = 0.0006), and 2-year OS (88.37% vs. 75.26%;  = 0.049) compared to BsAbs. NRM per 100 person-years was similar between two modalities (3.89 vs 3.86,  = 0.9871). CAR-T benefits persisted in third-line or later settings, as well as in analyses restricted to clinical trial data. Multivariate meta-regression confirmed CAR-T’s superiority for CR independent of median age. Safety analysis revealed CAR-T group had higher incidence of grade ≥3 neurotoxicity (7.48% vs. 0.23%,  = 0.0029), neutropenia (58.90% vs. 26.21%;  = 0007), thrombocytopenia (16.77% vs. 5.00%;  = 0.005), but lower incidence of grade ≥3 infection per 100 person-months (0.38 vs. 0.91,  = 0.040) than BsAb group. No differences were observed in grade ≥3 cytokine release syndrome or anemia.

[CONCLUSION] CAR-T therapy offered superior efficacy and survival in R/R indolent B-NHLs compared to BsAbs, albeit with increased AEs, highlighting the need for careful patient selection and toxicity management.

[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1186/s12967-025-07571-3.