Anti-CD3/CD20 bispecific antibodies as salvage therapy after CAR-T failure in relapsed/refractory large B-cell lymphoma: a systematic review and meta-analysis.

Patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) who experience disease progression following anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy face poor prognoses and limited therapeutic options. Bispecific antibodies (BsAbs) have emerged as a promising salvage strategy. This meta-analysis was conducted to evaluate the efficacy and safety of CD3×CD20 BsAbs in R/R LBCL patients after CAR-T failure. Clinical studies published between 2021 and 2025 were systematically reviewed, and a random-effects model was applied for pooled and subgroup analyses. A total of fifteen studies involving 1,169 patients were included. The pooled overall response rate (ORR) was 45% (95% CI, 37-53), while the complete response (CR) rate was 30% (95% CI, 25-35). Prior CAR-T exposure was associated with reduced BsAb efficacy compared to CAR-T-naïve patients (ORR: 45% vs. 69%, P = 0.039; CR: 30% vs. 45%, P = 0.020). Longer relapse intervals following CAR-T therapy correlated with improved efficacy: early relapse (≤ 90 days), intermediate relapse (91-180 days), and late relapse (181 days-1 year) yielded ORRs of 26%, 57%, and 71%, respectively (P = 0.0008), and CR rates of 10%, 29%, and 56%, respectively (P = 0.0005). Among the agents studied, epcoritamab demonstrated the highest ORR. In addition, combination regimens and subcutaneous administration showed superior responses compared to monotherapy and intravenous dosing. Cytokine release syndrome was the most common toxicity, predominantly grade 1-2, while neurotoxicity and hematologic adverse events were manageable. In conclusion, CD3×CD20 BsAbs exhibit meaningful efficacy and acceptable safety profiles in R/R LBCL patients following CAR-T failure, particularly in those with longer relapse intervals.