Objective: To report an uncommon and severe neurological immune-related adverse event (nirAE) of nivolumab and to provide an overview of the current literature on nirAEs of nivolumab.

Background: Immune checkpoint inhibitors (ICIs) targeting the anti-programmed death-1 antibody (anti-PD-1), such as nivolumab, are widely used for treating many cancers, including non-small cell lung cancer, renal cell cancer and melanoma. This new era of immunotherapy has been accompanied by a spectrum of adverse events. However, knowledge about neurologic irAEs in patients treated with ICI drugs is limited.

Method: We report a patient case where treatment with nivolumab against her small cell lung cancer led to encephalitis with choreoathetoid movements and include a systematic search of the literature in PubMed database.

Results: A 75-year-old woman treated with nivolumab (240 mg biweekly, seventeen cycles) for small cell lung cancer was admitted to the emergency room due to difficulties with balance and coordination. Neurological examination was consistent with encephalopathy in the form of inability to concentrate, dysarthria, hypomimia, involuntary purposeless and uncontrollable movements characteristic of chorea and athetosis in the whole body with a dominance on the right side. Magnetic resonance imaging of the brain demonstrated hyperintensities in subcortical regions of the brain including the basal ganglia bilateral. Analyses of the cerebrospinal fluid were normal. In the light of clinical and radiological findings, the patient was assumed to have a nivolumab-induced encephalitis with choreoathetosis. Initial treatment with intravenous immunoglobulins was ineffective. However urgent cessation of nivolumab therapy, plus treatment with high dose corticosteroids and immunotherapy with rituximab slowly reduced the involuntary movements.
Our review of clinical trials, case reports and case series reporting about neurological irAEs in cancer patients treated with anti-PD-1 shows that previously reported neurological irAEs of nivolumab were ataxia, encephalitis, Guillian-Barré syndrome, paraesthesia and seizures but no case of choreoathetosis has been published.

Conclusion: Neurological irAEs of nivolumab are rare and may be serious and life-threatening. Physicians need to be aware of the potential for nirAEs during treatment with ICIs, to ensure that diagnosis and treatment are expedited to prevent irreversible injury.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/nivolumab-induced-choreoathetosis-in-a-woman-with-lung-cancer-a-case-report-with-review-of-the-literature/