Overlap Syndrome of Myocarditis–Myositis– Myasthenia Induced by Immunotherapy in Advanced Melanoma: A Case Report

Immune checkpoint inhibitors have transformed the treatment of advanced melanoma; however, they may be associated with potentially severe immune-related adverse events. Among these, myocarditis–myositis– myasthenia overlap syndrome (MMM) is a rare but highly life-threatening condition. We report the case of an 84-year-old patient with stage IV melanoma treated with nivolumab and ipilimumab using a reduced-dose regimen, who initially developed immune-mediated hepatitis, followed by proximal muscle weakness, bulbar involvement, and myasthenic symptoms, associated with markedly elevated creatine kinase levels. During hospitalization, the patient developed complete atrioventricular block and significant troponin elevation, consistent with MMM overlap syndrome. Treatment with high-dose intravenous methylprednisolone followed by oral corticosteroids and pyridostigmine was initiated, resulting in favorable clinical evolution, with neurological improvement and hemodynamic stabilization without the need for second-line therapies. This case highlights the importance of early recognition of severe immune- related adverse events, the need for a multidisciplinary approach, and prompt initiation of immunosuppressive therapy, which may significantly improve clinical outcomes even in elderly patients.