Bispecific Antibodies Are Associated With Progressive Multifocal Leukoencephalopathy
Avi Gadoth1,2,3,4, Yael Paran2,3,4,5, Yair Mina1,2,4
1Department of Neurology, Tel Aviv Sourasky University Medical Center, Israel.
Neurology(R) Neuroimmunology & Neuroinflammation
|August 3, 2026
Summary
Progressive multifocal leukoencephalopathy (PML) is a rare but serious complication of bispecific antibodies (BisAbs) therapy in multiple myeloma (MM). Early recognition and prompt evaluation are critical for patients developing new neurologic symptoms during BisAbs treatment.
Area of Science:
- Neuro-oncology
- Immunology
- Hematology
Background:
- Bispecific antibodies (BisAbs) have revolutionized multiple myeloma (MM) treatment, but can cause immune perturbations like hypogammaglobulinemia and T-cell exhaustion, increasing infection risk.
- Progressive multifocal leukoencephalopathy (PML) is a rare, serious opportunistic infection associated with profound immune compromise.
Purpose of the Study:
- To report on patients with multiple myeloma (MM) who developed progressive multifocal leukoencephalopathy (PML) following bispecific antibody (BisAbs) therapy.
- To analyze clinical presentation, prior treatments, immune status, and outcomes in MM patients with BisAbs-associated PML.
Main Methods:
- Retrospective review of 5 MM patients who developed PML after BisAbs therapy (elranatamab, teclistamab, talquetamab).
- Evaluation of clinical data, neuroimaging, cerebrospinal fluid (CSF) studies, pathology, T-cell immunophenotyping, and antiviral T-cell responses.
- Analysis of JC virus (JCV) detection in CSF or brain biopsy.
Main Results:
- Five MM patients (median age 63) developed PML after BCMA-directed BisAbs therapy, with a median of 5 prior treatment lines.
- PML onset occurred a median of 12 months after BisAbs initiation; one patient developed it after only 2 prior therapies.
- JC virus (JCV) was detected in CSF (3/5) or brain biopsy (2/5); clinical symptoms included dysarthria, ataxia, and cognitive decline. Two patients showed specific anti-JCV/BKV T-cell responses despite immune compromise.
Conclusions:
- PML is a rare, life-threatening complication of BisAbs therapy in MM, potentially linked to BisAbs-related immune modulation independent of prior treatments.
- Early recognition of new neurologic symptoms in MM patients on BisAbs is crucial for prompt evaluation and management.
- Emerging therapies targeting JCV and immune checkpoint inhibitors may offer future treatment avenues for BisAbs-associated PML.
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