Concurrent Nivolumab-Induced Myocarditis and Myasthenia Gravis: A Case Report

Immune checkpoint inhibitors (ICIs) such as nivolumab have improved 10-year overall survival rates up to 43% in advanced melanoma. They carry a risk of severe immune-related adverse events (irAEs) up to 9%-33%, including cardiotoxicity and neuromuscular complications. Acral melanoma is a rare subtype that is often diagnosed late and requires aggressive therapy with adjunctive immunotherapy. Here, we report a rare case of an elderly male who developed myocarditis and myasthenia gravis 3 weeks after receiving the first dose of nivolumab for stage IIB acral melanoma.

A 72-year-old male with a late diagnosis of Stage IIB acral melanoma of the left great toe underwent toe amputation and received adjuvant therapy with nivolumab as per NCCN guidelines. Within 21 days after the first infusion, he developed chest pressure, fatigue, and diplopia. Workup revealed new-onset heart failure with an EF of 45%-50% with Grade 2 diastolic dysfunction, elevated troponin and NT pro-BNP, and cardiac MRI findings consistent with severe Grade 3, immune-related myocarditis. This presentation was complicated by a Mobitz Type 2 AV block, 10-s asystole, and therefore required permanent pacemaker placement. The symptoms of fatigue and diplopia led to a diagnostic workup with electromyography, confirming Grade 3 nivolumab-induced myasthenia gravis. He was treated with dexamethasone followed by a tapering dose of prednisone, and one cycle of IVIG at 0.4 g/kg for 5 days, leading to symptom resolution and improvement of EF to 60%-65%. However, 2 months later, he developed atrial fibrillation with a rapid ventricular rate, with device check showing 100% burden, therefore requiring hospitalization and subsequent cardioversion.

Nivolumab-induced myocarditis and myasthenia gravis require high clinical suspicion to make an early diagnosis and ICI discontinuation and aggressive immunosuppressive treatment. Due to early onset and rapid progression to conduction abnormalities and the development of new arrhythmogenic foci, immunotherapy-related myocarditis requires close monitoring. This case also highlights the importance of multidisciplinary management and individualized risk-benefit assessment when considering rechallenge with ICIs.