Viral Reactivation in Multiple Myeloma Patients Receiving Anti-BCMA Chimeric Antigen Receptor T-Cell Therapy

Chimeric antigen receptor T (CAR-T) cell therapy has become a standard of care for many hematological malignancies, and has significantly transformed treatment outcomes. However, CAR-T therapy is associated with specific toxicities, including infections. Although the anti-CD19 CAR-T risks are well-characterized, infectious complications following B-cell maturation antigen (BCMA)-directed CAR-T in multiple myeloma (MM) remain under-researched. In this study, we evaluated the incidence and clinical impact of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus (ADV) reactivations in 75 patients receiving anti-BCMA CAR-T for MM, and compared them to 60 patients receiving commercial anti-CD19 CAR-T for B-cell lymphoma (BCL). The viral reactivation rates were 20% for CMV and 8% for EBV in the MM group, vs. 31.7% and 3%, respectively, in the BCL group. No ADV reactivations were seen in either cohort. Most of the CMV reactivations (87% in the MM cohort and 68.5% in the BCL cohort) were asymptomatic and clinically insignificant, and had no impact on progression-free survival (PFS) or overall mortality. Overall, these findings suggest that although CMV and EBV reactivations are relatively common after anti-BCMA CAR-T, they are rarely associated with meaningful disease, and the risks do not exceed those of CD19-directed therapy. Thus, routine pre-emptive screening for these viruses may be unwarranted in asymptomatic patients.