Objective: To describe a delayed-onset rapidly progressive parkinsonian syndrome with encephalopathy following BCMA×CD3 bispecific antibody therapy.

Background: B-cell maturation antigen (BCMA) × CD3 bispecific antibodies (BsAbs) are an important treatment for relapsed or refractory multiple myeloma (RRMM). Cytokine release syndrome and early immune effector cell–associated neurotoxicity syndrome are recognized complications, but delayed movement disorders after BCMA×CD3 BsAb therapy remain poorly characterized.

Method: A 55-year-old woman with RRMM (International Staging System stage I; del[17p]) received linvoseltamab in September 2024 and achieved complete response by February 2025. Approximately 12 months after treatment initiation, she developed progressive bradykinesia and a short-stepped gait. Over the next three months, she developed cognitive decline, generalized rigidity, and severe weakness, leading to complete functional dependence. Neurological examinations showed hypokinetic-rigid parkinsonism, cognitive impairment with affective flattening and reduced spontaneous speech, hyperreflexia, and bilateral Babinski signs.

Results: Tc-99m TRODAT-1 SPECT revealed severe presynaptic dopaminergic deficits in the bilateral putamen and left caudate. Brain MRI demonstrated multifocal T2/FLAIR hyperintensities involving the periventricular and subcortical white matter and the pons. EEG showed generalized slowing. Cerebrospinal fluid revealed mildly elevated protein without pleocytosis. Infectious (including JC virus) and autoimmune/paraneoplastic studies were negative. Dopaminergic therapy was ineffective, and high-dose corticosteroids provided only transient improvement. The patient ultimately died from aspiration pneumonia complicated by septic shock.

Conclusion: This case describes a delayed-onset rapidly progressive parkinsonian syndrome with encephalopathy emerging one year after BCMA×CD3 bispecific antibody therapy. Rapid progression, poor levodopa response, presynaptic dopaminergic dysfunction, and multifocal CNS abnormalities suggest treatment-associated neuroinflammatory toxicity. Clinicians should be aware of potential delayed movement disorder manifestations with BCMA-targeted immunotherapies.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/delayed-onset-rapidly-progressive-parkinsonism-after-bcmaxcd3-bispecific-antibody-therapy-a-case-report/