Background: In the era of precision medicine, immune checkpoint inhibitors (ICIs) have dramatically changed the therapeutic approach toward advanced cancers. Despite an undeniably therapeutic benefit, ICIs have unique and uncharted toxicities known as immune-related adverse events (irAEs). Case Presentation: We report a rare overlap syndrome of inflammatory and necrotizing myopathy with a superimposed myasthenia-like syndrome in a melanoma patient who had received the first dose of pembrolizumab 22 days before symptoms onset. The patient initially presented with muscle weakness and ptosis and rapidly progressed to tetraparesis, extrinsic ophthalmoplegia, dysarthria, dysphagia, and respiratory difficulty with a short-term need for non-invasive ventilation and nasogastric intubation. Transitory myocarditis was also diagnosed. One month after hospital discharge, the patient still exhibits mild dysarthria, dysphagia, and ptosis and needs walking assistance. Conclusion: Although rare, neuromuscular irAEs impose a notable burden on morbidity and even mortality. Early recognition of symptoms and prompt intervention are crucial for the management of immunotherapy-related toxicity.

Keywords: Immune checkpoint inhibitors, immune-related adverse events, pembrolizumab, metastatic melanoma, myosistis, myasthenic-like syndrome.