Triple M Overlap Syndrome After Immune Checkpoint Inhibitors: A Case Series of a High-Mortality Phenotype

Immune checkpoint inhibitor-associated Triple M overlap syndrome (TMOS), defined by concurrent myocarditis, myositis, and myasthenia gravis, is a rare but life-threatening immune-related adverse event. We report a single-center case series of 8 consecutive patients who developed TMOS during immune checkpoint inhibitor therapy for solid malignancies between 2023 and 2025. Median age was 76 years and median time to symptom onset was 14.5 days after exposure. All patients had myositis symptoms; 5 required mechanical ventilation and 1 subsequently required tracheostomy. Cardiac involvement was characterized by troponin elevation and frequent electrical abnormalities, including complete atrioventricular block, ventricular tachyarrhythmias, and bundle branch block, despite preserved left ventricular systolic function on imaging. Corticosteroid monotherapy was insufficient in practice, and all patients required additional immunomodulatory therapy. TMOS requires early recognition, close monitoring, and rapid multidisciplinary escalation of care.