Vaccination in Multiple Myeloma: Challenges and Strategies

ABSTRACT Background Multiple myeloma (MM) is a hematological malignancy characterized by profound immunosuppression resulting from both disease‐related mechanisms and treatment‐induced immune dysfunction. This compromised immune status markedly increases susceptibility to infections, a leading cause of morbidity and mortality in MM patients. While vaccination represents a cornerstone of infection prevention, standard immunization strategies often yield suboptimal responses in this population. Objectives This review synthesizes current evidence on the immunological barriers and clinical effectiveness of vaccination in MM. We evaluate vaccines targeting influenza, Streptococcus pneumoniae , SARS‐CoV‐2, and other relevant pathogens, and explore determinants influencing vaccine efficacy, including optimal timing, formulation, and patient‐specific immune parameters. Methods A comprehensive literature review was conducted, encompassing clinical trials, retrospective cohort studies, expert consensus guidelines, and population‐based data. Extracted outcomes included serological responses, infection‐related events, and vaccine safety in MM patients. Results Patients with MM exhibit impaired vaccine responses due to hypogammaglobulinemia, T‐ and B‐cell dysfunction, and therapy‐induced lymphodepletion. Despite modest immunogenicity, influenza and pneumococcal vaccines reduce respiratory infections and hospitalizations. Sequential administration of PCV13 followed by PPSV23, as well as post‐autologous stem cell transplantation (ASCT) three‐dose regimens, is associated with reduced pneumonia incidence. COVID‐19 vaccines elicit variable responses, particularly in patients on anti‐CD38 or BCMA‐targeted therapies, highlighting the need for booster doses and, in selected cases, prophylactic monoclonal antibodies. Vaccines against herpes zoster, hepatitis B, and Haemophilus influenzae type B are also recommended, particularly around ASCT. Immunophenotypic markers such as CD19+ B‐cell and CD4+ T‐cell counts are predictive of vaccine responsiveness, supporting immune profiling as a tool for individualized vaccination planning. Conclusions Vaccination remains a critical component of infection prevention in MM. Although immunogenicity may be attenuated, clinical benefits—namely, reduced infection burden and healthcare utilization—support broad vaccine implementation. A personalized approach, considering the treatment phase, disease control, and immune status, is essential to optimize vaccine effectiveness. Ongoing research into high‐dose, adjuvanted, and next‐generation vaccines is critical to enhance protection in this vulnerable population.