Infectious toxicities associated with bispecific antibodies and CAR-T Cells in multiple myeloma: a systematic review

Abstract T-cell–redirecting therapies have transformed the treatment of relapsed/refractory multiple myeloma (RRMM) but are associated with substantial infection risk. We systematically reviewed infections after CAR T-cell therapy and bispecific antibodies (BsAbs), focusing on incidence, timing, pathogens, risk factors, and prevention. Following PRISMA guidelines, we searched PubMed through May 22, 2026, and included studies reporting infectious outcomes in RRMM patients treated with CAR-T cells or BsAbs. A total of 123 predominantly early-phase, non-comparative studies were analyzed. Across BCMA-directed CAR-T products and BsAbs, infections were frequent (any-grade incidence ~ 40–80%), with highest risk early after CAR-T infusion and during the first months of BsAb therapy. Grade ≥ 3 infections were common and exceeded 50% in several BsAb cohorts. Fatal infections were less frequent but occurred across both CAR-T and BsAb studies. In randomized CAR-T trials, grade 5 infections represented a substantial proportion of treatment-related deaths. Talquetamab showed lower infection rates (47–55%) but relevant mucocutaneous toxicity. Viral and bacterial pathogens predominated; CMV reactivation, invasive fungal infections, and Pneumocystis jirovecii pneumonia, particularly without prophylaxis, were also reported. Risk factors included neutropenia, corticosteroid/tocilizumab exposure, and hypogammaglobulinemia. Antiviral and Pneumocystis jirovecii pneumonia (PJP) prophylaxis and, most notably, immunoglobulin replacement reduced infections, though residual risk persisted. Real-world data suggest higher infection-related healthcare use and mortality with BsAbs versus CAR-T therapy. Extended dosing intervals may reduce infections, particularly severe infections, while preserving efficacy. Infectious toxicity remains a key limitation. Risk is particularly high with BCMA-targeted therapies and continuous BsAb administration. Tailored prophylaxis, early immunoglobulin replacement, and response-adapted treatment strategies, including extended dosing intervals, may improve safety and outcomes.