Myasthenia Gravis Lambert-Eaton overlap syndrome induced by nivolumab in a metastatic melanoma patient.

Abstract

Myasthenia gravis (MG) Lambert-Eaton (LE) overlap syndrome is a rare condition. Here, we describe the first caseof MG-LE overlap syndrome revealed by the anti-programmed cell death 1 inhibitor, nivolumab, in a patient treatedfor metastatic melanoma. Three months after receiving nivolumab and 1 month after brain metastasis radiotherapy, our patient developedgeneralized fatigue with intermittent ptosis and swallowing difficulty suggesting a myasthenic syndrome.Electromyogram findings, anti-acetylcholine receptor, and anti-calcium channel antibodies levels were consistentwith an immune-related myasthenic syndrome with specific features for both MG and LE syndromes.Immunotherapy with nivolumab was stopped. Patient was treated with systemic immunosuppressive and anti-cholinesterasedrugs, with remarkable improvement of his neurological symptoms. Prolonged partial remission wasobtained for his metastatic melanoma without need for a third-line treatment. Two years later, a relapse of hismyasthenic symptoms was observed along with new neurological symptoms related to brain radiation necrosis. We describe the first case of MG-LE overlap syndrome diagnosed after anti-PD1 immunotherapy for metastaticmelanoma, which appeared after radiation therapy and then relapsed after brain radiation necrosis. Wehypothesized a role for brain inflammation as a trigger for MG-LE onset. Neuro-muscular junctions disease inducedor revealed by checkpoint inhibitors can be challenging and requires long-term follow-up.