Background: Relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) remains a clinical challenge with limited treatment options after failure of chemo-immunotherapy. Bispecific antibodies (BsAbs) represent a novel immunotherapeutic class that redirects T cells against malignant B cells and have demonstrated promising efficacy in early-phase trials.

Methods: We conducted a systematic review of published clinical trials evaluating bispecific antibody therapies in patients with R/R DLBCL. Electronic databases including PubMed, Embase, Scopus, Web of Science, and ClinicalTrials.gov were searched from 2010 to 2025. Inclusion criteria was studies reporting efficacy and/or safety outcomes in R/R DLBCL patients treated with bispecific antibodies. Overall response rate (ORR), complete response rate (CRR), and safety outcomes were pooled using a random-effects meta-analysis of proportions.

Results: Twelve eligible studies involving 744 patients were included, primarily evaluating glofitamab (6 studies), epcoritamab (2), mosunetuzumab (2), and odronextamab (2). The pooled ORR was 53.3% (95% CI 45.9–60.6%), and pooled CRR was 36.6% (95% CI 28.5–45.4%). Progression-free survival (PFS) ranged from 2 to 5.3 months, while median overall survival (OS) extended from 4 to 14.9 months across studies. Cytokine release syndrome (CRS) was reported in 22–83% of patients, predominantly low grade, with Grade ≥3 CRS occurring in ≤9.3%. Conclusions: Bispecific antibodies offer a promising therapeutic approach for relapsed/refractory DLBCL, particularly in heavily pretreated or CAR-T-ineligible patients. These findings support their expanding role in clinical practice and highlight the need for further real-world evidence. Multi-national randomized controlled trials with longer follow-up are needed to establish durability and optimize treatment sequencing.

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2025
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