Practical recommendations for infectious prophylaxis and vaccination in multiple myeloma patients

Infections remain a major cause of morbidity and mortality in multiple myeloma (MM), driven by the interplay between disease-induced immune dysfunction and treatment-related immunosuppression. The introduction of proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, bispecific antibodies, and chimeric antigen receptor T (CAR-T) cell therapy has markedly improved survival while simultaneously reshaping the infectious risk landscape. Different treatment strategies compromise immunity in distinct mechanisms. Conventional chemotherapy and some targeted agents primarily increase the risk of bacterial infections through neutropenia. Modern immunotherapies, however, produce profound and prolonged hypogammaglobulinemia alongside cellular immune deficits, predisposing patients to viral reactivation and opportunistic infections. BCMA-targeting therapies (particularly bispecific antibodies and CAR-T cells) cause sustained plasma cell depletion and durable humoral immune impairment, resulting in an infection pattern that can persist well beyond treatment completion. Effective prevention requires a risk-stratified approach accounting for disease stage, treatment regimen, cumulative immunosuppression, and individual patient characteristics. This review synthesizes current evidence and provides practical, treatment-specific recommendations spanning infection risk assessment, pre-treatment screening, antimicrobial and antifungal prophylaxis, antiviral strategies, immunoglobulin replacement, granulocyte colony-stimulating factor use, and vaccination. Emphasis is placed on bispecific antibodies and CAR-T cell therapies, where infectious risk is greatest and prophylactic strategies are evolving most rapidly. Immunoglobulin replacement is highlighted as an increasingly relevant supportive strategy, with recent observational studies linking its use to marked reductions in serious infections and, among recipients of anti-BCMA bispecific antibodies, improved survival. This review provides clinicians with a practical framework for individualized infection prevention in the evolving therapeutic landscape of MM.