Progressive multifocal leukoencephalopathy associated with elranatamab therapy in relapsed/refractory multiple myeloma

IntroductionElranatamab, a bispecific antibody targeting B-cell maturation antigen (BCMA) and CD3, has demonstrated remarkable efficacy in relapsed or refractory multiple myeloma (RRMM). With the growing clinical use of BCMA-directed bispecific antibodies, their safety profile continues to evolve; however, progressive multifocal leukoencephalopathy (PML) has not been systematically described with elranatamab to date.Case ReportA 67-year-old woman with RRMM achieved a complete response following elranatamab therapy. After the seventh treatment cycle, she developed neurological symptoms including dysarthria and gait disturbance. Brain magnetic resonance imaging revealed multifocal, non-enhancing white-matter lesions, and cerebrospinal fluid polymerase chain reaction confirmed JC virus infection, establishing the diagnosis of PML.Management and OutcomeElranatamab was discontinued immediately. Despite treatment with intravenous immunoglobulin, mirtazapine, and compassionate-use nivolumab, her neurological status progressively worsened, necessitating intubation and intensive care management.DiscussionThis case suggests a probable association between elranatamab therapy and JC virus reactivation leading to PML. The pathogenesis is likely multifactorial, reflecting both prior cumulative immunosuppression and elranatamab-induced plasma-cell depletion with resultant hypogammaglobulinemia. Clinicians should maintain vigilance for new or unexplained neurological manifestations in patients receiving BCMA-directed T-cell-redirecting therapies. Early neuroimaging and cerebrospinal fluid JC virus testing, combined with proactive immunoglobulin replacement and systematic pharmacovigilance, are essential for timely diagnosis and improved outcomes. Overall, this case highlights the need for early JC virus monitoring and awareness of delayed neuroinfectious complications associated with BCMA-targeted immunotherapies.