Bispecific antibodies (BsAbs) represent a promising advancement in the treatment of multiple myeloma (MM), particularly for relapsed or refractory cases. However, their use is associated with a high risk of infections due to both the immunosuppressive nature of MM and the mechanism of BsAbs themselves. Studies report infection rates up to 56% with BsAb therapy, with severe infections in nearly a quarter of patients. Viral infections are most common, followed by bacterial and fungal. Risk factors include hypogammaglobulinemia, neutropenia, prior treatment intensity, and high disease burden. Preventive strategies, including prophylaxis with antivirals, antibiotics, antifungals, and pneumocystis jiroveci pneumonia (PJP) prophylaxis, as well as immunoglobulin replacement and granulocyte-stimulating factor use, are recommended—particularly in patients with profound neutropenia or those receiving high-dose steroids.

Despite these guidelines, infections remain a major challenge, especially as many BsAbs are still under early-phase evaluation. Clinical trials have shown higher infection rates with B-cell maturation antigen-targeted BsAbs, particularly when used in combination regimens. Pneumonia, respiratory tract infections, and opportunistic infections such as CMV and PJP are frequently reported. Vigilant screening, individualized risk assessment, and consistent implementation of prophylaxis are critical. As BsAbs become more integrated into MM treatment, optimizing infection control will be essential for improving patient safety and therapeutic success.

Reference: Alshammari F, Alrajhi AM, Howaidi J. Risk of infections in bispecific antibody therapy for multiple myeloma: a comprehensive review of literature. Hematology. 2025;30(1):2448898. doi: 10.1080/16078454.2024.2448898.