Confirmed Myocarditis-Myositis Overlap Without Myasthenia Gravis: Evaluating for Triple M Syndrome Following Combined Enfortumab Vedotin and Pembrolizumab Therapy.

Authors

Bryan Ashong, Yash Ranga

Published in

Cureus. Volume 18. Issue 9. Pages e116849. Epub Sep 24, 2026.

Abstract

A 64-year-old male with Stage III urothelial carcinoma of the right ureter presented to the emergency department 3 weeks after a single cycle of combined enfortumab vedotin and pembrolizumab with chest tightness, neck weakness, drop head, and myalgias. Laboratory findings included markedly elevated high-sensitivity troponin I, creatine phosphokinase, lactate dehydrogenase, and transaminases. Electrocardiography showed anterolateral ST depression and left anterior fascicular block, which was new as compared to a prior tracing. He was managed in the cardiovascular intensive care unit. Cardiac catheterization revealed concurrent 90% mid-left anterior descending artery stenosis, treated with drug-eluting stent placement. Endomyocardial biopsy confirmed focal moderate lymphocytic myocarditis. Cardiac MRI demonstrated mildly reduced biventricular function and a non-ischemic pattern of late gadolinium enhancement consistent with myocarditis sequelae. Given the overlapping multisystem presentation, a multidisciplinary team (cardiology, neurology, and oncology) elected to treat with high-dose methylprednisolone (1 g QOD x 5 days), the guideline-recommended first-line therapy for ICI-associated myocarditis, and intravenous immunoglobulin (400 mg/kg QOD x 5 days), with biochemical improvement. IVIG was added given clinical concern for possible neuromuscular junction involvement in the setting of concurrent myositis and possible overlap syndrome, reflecting a precautionary approach to a potentially rapidly progressive presentation. Myasthenia gravis was considered but not confirmed: repeated neurological examinations demonstrated no fatigable weakness, and serology was negative for acetylcholine receptor binding and muscle-specific kinase antibodies. Both implicated agents were permanently discontinued. This case illustrates the spectrum and severity of multisystem immune-related toxicity from combined antibody-drug conjugate and immune checkpoint inhibitor therapy.

PMID:
42927390
Bibliographic data and abstract were imported from PubMed on 25 Oct 2026.

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