Work

Progressive multifocal leukoencephalopathy, bispecific antibodies, and multiple myeloma: a case report and systematic review of the literature

Year: 2026

Type: review

Abstract: Background Bispecific antibodies (BsAbs) have transformed outcomes in relapsed/refractory multiple myeloma (RRMM) but carry a substantial, sustained infectious burden, including rare cases of progressive multifocal leukoencephalopathy (PML). Methods We present an index case of a patient with RRMM treated with BsAbs diagnosed with PML complicated by immune reconstitution inflammatory syndrome (PML-IRIS) and perform a systematic review of the literature contextualizing this case among all published reports of PML and PML-IRIS following BsAb therapy in multiple myeloma (MM). Case presentation We report a 65-year-old woman with triple-class-refractory λ light-chain MM who was sequentially treated with the anti-B-cell membrane antigen (BCMA)×CD3 BsAb elranatamab and, subsequently, the anti-GPRC5D×CD3 BsAb talquetamab. During the second cycle of talquetamab, she developed rapidly progressive confusion, visual disturbance, and generalized tonic–clonic seizures. Cerebrospinal fluid JC virus (JCV) polymerase chain reaction (PCR) was negative on two occasions despite a clinical and radiographic course highly suggestive of PML; brain biopsy confirmed PML-IRIS. Despite talquetamab discontinuation, IVIG, mirtazapine, and compassionate-use nivolumab, the patient achieved only transient neurological stabilization and died 2 months after presentation. Results A systematic review of the literature identified 16 additional sources describing 29 patients with PML or PML-IRIS following BsAb therapy for MM, confirmed on full-text review to represent distinct individuals with no duplication between reports. BCMA-directed constructs accounted for most implicated agents, and talquetamab was implicated only in patients with prior or concurrent BCMA-directed exposure. PML-IRIS was documented in two of these patients and could not be excluded in a third. Despite uniformly supportive management, PML-attributable mortality was 89% (25/28) among patients with a definitive reported outcome, including the index case. Conclusion PML, and PML-IRIS specifically, is an emerging, likely class-level complication of BsAb therapy in MM. Clinicians should maintain a low threshold for neuroimaging and CSF JCV testing. These findings should be interpreted in light of the substantial clinical benefit that BsAbs provide in this heavily pretreated population.

Source: Frontiers in Oncology

DOI: 10.3389/fonc.2026.1935696