Cytomegalovirus infection in patients receiving bispecific antibodies for multiple myeloma and B-cell malignancies: a single-center cohort and meta-analysis.

BACKGROUND: Bispecific antibodies (BsAbs) are transformative therapies for multiple myeloma (MM) and B-cell malignancies. Cytomegalovirus (CMV) infection has been reported as a potential complication of unclear clinical magnitude. METHODS: We conducted a retrospective study of MM patients treated with BsAbs at our institution (2020-2025), alongside a systematic review and meta-analysis of clinical trials and observational studies evaluating BsAbs for MM, B-cell lymphoma, and acute lymphoblastic leukemia. Study outcomes included clinically significant CMV infection (csCMVi), any CMV DNAemia, and CMV disease. RESULTS: Our cohort included 98 BsAb therapy courses (74.5% anti-B-cell maturation antigen [BCMA]) with a median follow-up of 10.4 months. Cumulative incidence rates for csCMVi and CMV disease were 9.2% (9/98) and 3.1% (3/98), respectively. Factors associated with csCMVi at the univariable level were poorer functional status, prior allogeneic hematopoietic stem cell transplantation (allo-HSCT), grade 4 neutropenia, and grade ≥3 cytokine release syndrome (CRS). The meta-analysis (23 studies plus our single-center cohort comprising 2,956 BsAb courses) revealed a pooled cumulative incidence rates of 9% (95% confidence interval [CI]: 4-15%; I2 96.11%) for csCMVi and 1% (95% CI: 0-2%; I2 69.78%) for CMV disease. Incidence was notably higher in studies applying routine CMV DNAemia monitoring and with anti-BCMA agents. CONCLUSION: The occurrence of csCMVi or CMV disease during the course of BsAb therapy for MM or B-cell malignancies is uncommon, arguing against routine CMV DNAemia monitoring or antiviral prophylaxis. Prevention approaches, however, may be warranted in patients receiving anti-BCMA BsAbs with additional risk factors such as allo-HSCT or severe CRS. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD420251162657.