ArticleExperimental and therapeutic medicine2026
Immune checkpoint inhibitor-induced myocarditis with myositis and/or myasthenia gravis overlap syndrome: A case series.
Article in Experimental and therapeutic medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Immune checkpoint inhibitors (ICIs) can lead to immune-related adverse events, including myocarditis with myositis and/or myasthenia gravis overlap syndrome (IM3OS). This syndrome poses notable management challenges and has high mortality rates. Due to limited data, its clinical features and optimal treatment strategies remain poorly understood. The present study aims to clarify these aspects and share clinical management experiences. A total of 6 patients with IM3OS were retrospectively analyzed, collecting demographic, clinical, laboratory, electrophysiological, therapeutic and outcome data. Additionally, the relevant literature was reviewed to contextualize the findings. The 6 patients, all male, with a median age of 70.5 years (range, 63-83 years), developed symptoms a median of 30.5 days post-ICI initiation. Common symptoms included fluctuating ptosis, neck weakness, fatigue, myalgia, diplopia, dysphagia, dysarthria and limb weakness. Of the 6 patients, 3 required ventilation support. Elevated creatine kinase (CK) and cardiac troponin I (cTnI) were observed in all patients, with CK and cTnI levels decreasing rapidly post-treatment. Cardiac troponin T levels remained elevated for 3 months. Myotonic discharge and increased jitter were noted in 2 patients. Treatments included corticosteroids, intravenous immunoglobulin (IVIG), plasmapheresis and rituximab. Pyridostigmine was discontinued in 2 out of 4 patients due to severe cardiac adverse effects. Despite interventions, 2 patients died and 1 was bedridden, with only 3 showing favorable outcomes. In conclusion, IM3OS has a high fatality rate, highlighting the need for prompt intervention in ICI-treated patients with neuromuscular symptoms. Serum cTnI is a reliable cardiac injury marker, and early treatment with IVIG, plasmapheresis and high-dose methylprednisolone is recommended. Pyridostigmine should be administered with caution in patients with IM3OS, particularly in the presence of bradyarrhythmic ICI-related myocarditis. Given the high mortality and disability rates associated with IM3OS, novel biological targeted therapies such as eculizumab and efgartigimod may reduce fatal outcomes.
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