Vinicius S. Marra

Background: Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the treatment of relapsed/refractory multiple myeloma but is associated with significant infectious complications due to prolonged immunosuppression, cytopenias, and immune dysfunction. Objective: To systematically evaluate the incidence, timing, microbiologic patterns, and risk factors of infectious complications in patients with multiple myeloma undergoing anti-BCMA CAR-T cell therapy. Study design: Systematic review following PRISMA guidelines. We searched PubMed, EMBASE, Scopus, CINAHL, Cochrane Library, and Google Scholar through February 2025. Eligible studies included cohorts, phase II and III trials, and case-control studies reporting infections after CAR-T therapy. Data were extracted independently and quality assessed with the Downs and Black scale. Owing to heterogeneity, results were synthesized descriptively. Etiology and temporal patterns were analyzed at the event level. Results: Nineteen studies published between 2021 and 2025, including 1,495 patients with multiple myeloma treated with CAR T-cell therapy, were included. Infection incidence ranged from approximately 33% to over 70%. Bacterial infections predominated, particularly during the first 30 days after infusion, whereas viral infections increased during later follow-up. Fungal infections were less frequent. Rates of severe infection varied widely (5% to 60%), and infection-related mortality ranged from 0% to over 5%. Key risk factors included prolonged cytopenias, low CD4 ⁺ T-cell, and hypogammaglobulinemia. Conclusions: Infectious complications following CAR-T cell therapy in multiple myeloma are frequent, with distinct early and late microbiologic profiles. Standardized infection definitions, harmonized surveillance, and risk-stratified prevention strategies are essential to reduce infection-related morbidity while preserving the benefits of this therapy.