Immune Checkpoint Inhibitor-Induced Myositis Myocarditis and Myasthenia Gravis (MMM) Overlap Syndrome in a Rural...

Immune checkpoint inhibitors (ICIs) are commonly used for the treatment of some advanced cancers. Although effective, they can cause side effects. This case series describes four patients treated for ICI-induced myositis, myocarditis and myasthenia gravis (MMM) overlap syndrome at a rural general hospital in the United Kingdom between 2023 and 2025. To the best of our knowledge, this is the first open-access case series describing its management specifically in a rural, low-resource setting. Patients were exclusively male with a mean age of 68.9 years and had received either dual nivolumab/ipilimumab or pembrolizumab monotherapy for metastatic melanomas, renal cell carcinoma or synchronous oesophageal and lung cancer. Symptoms included fatigue, proximal muscle weakness, dysphagia, diplopia, and dyspnea. High-dose intravenous methylprednisolone was the mainstay of treatment, with additional immunomodulators like mycophenolate mofetil, tocilizumab, tacrolimus and intravenous immunoglobulins added based on clinical progression and specialist input. Two patients recovered with treatment and remained progression free following ICI discontinuation, while two patients died due to respiratory failure, likely related to delayed initiation of myasthenia gravis-directed therapy. Prominent bulbar symptoms at presentation and high myasthenia gravis composite scores appear to correlate with poor outcomes. Early access to diagnostics such as autoantibodies for MG, tissue biopsy and electrodiagnostics was often limited by logistical barriers. However, biomarkers like creatine kinase, troponins and imaging modalities were consistently available. This series highlights the challenges of managing MMM syndrome in non-specialist resource-limited settings and the potential dangers of delayed immunosuppression. A high index of suspicion, early multidisciplinary involvement, and rapid initiation of therapies are critical to improving outcomes. Furthermore, this case series supports the need for simplified, context-appropriate guidelines that prioritise clinically impactful investigations and also highlights the emerging potential of the neutrophil-to-lymphocyte ratio as a practical prognostic tool. As ICI indications expand, awareness of MMM overlap syndrome among frontline clinicians is essential to reduce treatment delays and prevent avoidable mortality.