Safety Landscape of Bispecific Antibody Therapy in Non-Hodgkin Lymphoma: A Systematic Review and Meta-Analysis

• Infections occur in 38% of patients with NHL treated with bispecific antibodies, with 12% experiencing grade ≥3 infections.

• The rate of all grade CRS with bispecific antibodies is 48%, but grade ≥3 CRS is rare accounting for 2% of reported cases.

Bispecific antibodies (BsAbs) have emerged as a novel immunotherapy option for the treatment of non-Hodgkin lymphoma (NHL), however, their safety profiles remain underexplored. We conducted a systematic review and meta-analysis to better delineate the safety profiles of BsAbs, focusing on the prevalence and rates of infection, neutropenia, cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). A comprehensive literature search led to the inclusion of 32 trials with a total of 2192 patients. Median age of participants was 66 years (range: 55 – 84 years) with a median of 2 prior lines of therapy (range: 0-5). At a median follow-up of 9.4 months (range: 2.8 – 32 months), the pooled prevalence of all-grade and grade ≥3 neutropenia was 38% and 26%, respectively, while all-grade and grade ≥3 infections occurring at a rate of 38% and 12%, respectively. The prevalence of all grade CRS was 48% but only 2% was grade ≥3, while ICANS was infrequent (5% all grade). Stratification revealed both increased all-grade neutropenia and infection rates with combination therapy in comparison to BsAbs monotherapy. Despite these variations, BsAbs demonstrated an overall manageable safety profile, suggesting their viability as a treatment option in the relapsed/refractory setting. Standardized safety reporting and vigilant monitoring are essential to optimize their clinical use and improve patient outcomes.