Infection Risk Management and Prophylactic Strategies for Patients with R/R MM

Dr. Costa addresses the primary clinician concern regarding BCMA-directed T-cell engagers: infection risk. Early trials including MagnetisMM-3 and MajesTEC-1, accruing patients during 2020 through 2022, demonstrated prominent infection signals during the pandemic era before standard mitigation strategies existed. Recent experience in larger trials shows substantially improved outcomes, reflecting better understanding and enhanced strategies.

Dr. Costa emphasizes critical infection risk mechanism concepts. Oncologists traditionally associate infection risk with neutropenia from cytotoxic chemotherapy, but bispecific-related risk extends beyond neutropenia. Although these agents cause neutropenia, this effect is transient and growth factor-responsive. More concerning infections occur later when patients are not neutropenic.

Primary risk stems from profound humoral immunodeficiency. BCMA-directed therapy patients develop severe hypogammaglobulinemia because normal plasma cells express BCMA, and effective targeting eliminates immunoglobulin production. Dr. Costa advocates proactive universal intravenous immunoglobulin (IVIG) replacement at first cycle end. Additional measures include antibiotic prophylaxis with levofloxacin or trimethoprim-sulfamethoxazole during the first month before IVIG initiation.

Comprehensive strategies include universal Pneumocystis jirovecii pneumonia prophylaxis with trimethoprim-sulfamethoxazole 3 times weekly and antiviral prophylaxis with acyclovir. Multiple published guidelines exist from International Myeloma Working Group and consortiums. Importantly, fever during the first week represents cytokine release syndrome, rather than infection, whereas fever beyond the second week should be considered infection until proven otherwise, requiring aggressive assessment.