Bispecific antibodies, a novel immunotherapy for multiple myeloma, create immune synapses between T-cell marker CD3 and malignant cell markers like B-cell maturation antigen (BCMA), FcRH5, and GPRC5D, effectively depleting plasma cells and some T-cells, which increases infection risk. A systematic review and meta-analysis of 16 clinical trials with 1666 patients showed a pooled all-grade infection prevalence of 56% and grade ≥3 infections at 24%. BCMA-targeted bispecifics had higher severe infection rates than non-BCMA bispecifics (25% vs 20%), and combination therapies showed higher infection rates than monotherapies (71% vs 52%). 

The review identified a high prevalence of infections in patients treated with bispecific antibodies, with higher risks in BCMA-targeted and combination therapies. Analyzing 16 clinical trials and 4 observational studies, it found severe infections were more common in BCMA-targeted therapies. Combination therapies had higher all-grade infection rates, likely due to more comprehensive plasma cell depletion. The review underscores the importance of antimicrobial prophylaxis, including herpes simplex, varicella zoster, and Pneumocystis jirovecii pneumonia prophylaxis, along with pretreatment screening for hepatitis B and cytomegalovirus. It suggests that patients on bispecific antibody combination therapies require closer monitoring and targeted prophylaxis to manage heightened infection risk.

Reference: Reynolds G, Cliff ERS, Mohyuddin GR, et al. Infections following bispecific antibodies in myeloma: a systematic review and meta-analysis. Blood Adv. 2023;7(19):5898-5903. doi: 10.1182/bloodadvances.2023010539.