Objective: To outline a novel immunologically-mediated neurological adverse event associated with the use of a medication class which has an expanding range of applications [1].

Background: Pembrolizumab is a humanized monoclonal antibody which blocks the programmed cell death protein-1 (PD-1) receptor and is used in a range of malignancies [1,2]. Pembrolizumab has been associated with a range of neurological adverse events and myoclonus is not a recognised adverse event [3,4]. A 77-year-old, right-handed, retired engineer presented with disabling involuntary movements which had progressed over days to involve both upper limbs and the muscles of facial expression, left more than right. He had no cognitive symptoms. His recent medical history was notable for having completed four cycles of pembrolizumab for metastatic prostate cancer. There was no family history of note and the patient had an excellent functional baseline.

Method: We observed sudden, brief muscle jerks involving the upper limbs and face bilaterally, which were involuntary, triggered by action, and consistent with a multifocal myoclonus. The rest of the neurological examination was normal. A rigorous metabolic, inflammatory and infective screen failed to identify a cause. An extensive panel of paraneoplastic antibodies was negative. Electroencephalogram showed no ictal correlate. MRI Brain with diffusion-weighted imaging was unremarkable.

Results: We treated this patient symptomatically with oral clonazepam with minimal benefit. We then instituted intravenous methylprednisolone, followed by a slow oral prednisolone taper. The patient demonstrated an excellent clinical response to this treatment strategy.

Conclusion: We report a case of a subacute movement disorder in a patient treated with pembrolizumab for metastatic prostate cancer, which proved to be highly steroid-responsive. This is a novel immunologically-mediated neurological adverse event associated with the use of a medication class which has an expanding range of applications.

References: [1] McDermott, J. & Jimeno, A. Pembrolizumab: PD-1 inhibition as a therapeutic strategy in cancer. Drugs Today (Barc) 51, 7-20, doi:10.1358/dot.2015.51.1.2250387 (2015). [2] Longoria, T. C. & Tewari, K. S. Evaluation of the pharmacokinetics and metabolism of pembrolizumab in the treatment of melanoma. Expert opinion on drug metabolism & toxicology 12, 1247-1253, doi:10.1080/17425255.2016.1216976 (2016). [3] Cuzzubbo, S. et al. Neurological adverse events associated with immune checkpoint inhibitors: Review of the literature. Eur J Cancer 73, 1-8, doi:10.1016/j.ejca.2016.12.001 (2017). [4] Kao, J. C. et al. Neurological Complications Associated With Anti-Programmed Death 1 (PD-1) Antibodies. JAMA Neurol 74, 1216-1222, doi:10.1001/jamaneurol.2017.1912 (2017).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/steroid-responsive-myoclonus-in-the-context-of-pembrolizumab-treatment-a-novel-neurological-phenotype/