Safety landscape of bispecific antibody therapy in non-Hodgkin lymphoma: a meta-analysis

Bispecific antibodies (BsAbs) have emerged as a novel immunotherapy option for the treatment of non-Hodgkin lymphoma; 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) 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 , the pooled prevalence of all-grade and grade ≥3 neutropenia was 38% and 26%, respectively, with 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, whereas 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.