Confirmed Myocarditis-Myositis Overlap Without Myasthenia Gravis: Evaluating for Triple M Syndrome Following Combined Enfortumab Vedotin and Pembrolizumab Therapy.
- 1Anesthesia, University of South Florida Morsani College of Medicine, Tampa, USA.
- 2Internal Medicine, Jawaharlal Nehru Medical College, Ajmer, IND.
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.
Related
- Management of extravasations of enfortumab vedotin and pembrolizumab: a case report and mini review of the current literature
- Skin toxicity and effectiveness of first-line enfortumab vedotin plus pembrolizumab for urothelial carcinoma: a prospective multicenter real-world study in Japan.
- Circulating Tumor DNA Clearance Is Associated with Response and Survival in Metastatic Urothelial Carcinoma Treated with First-Line Enfortumab Vedotin Plus Pembrolizumab
- Case Report: Fulminant sintilimab-associated myocarditis complicated by complete atrioventricular block and suspected myositis-myasthenia gravis overlap syndrome
- Skin Toxic Effects and Survival With Enfortumab Vedotin-Pembrolizumab in Advanced Urothelial Carcinoma.
BibTeX
@article{ashong2026confirmed,
title = {{Confirmed Myocarditis-Myositis Overlap Without Myasthenia Gravis: Evaluating for Triple M Syndrome Following Combined Enfortumab Vedotin and Pembrolizumab Therapy.}},
author = {Bryan Ashong and Yash Ranga},
journal = {Cureus},
year = {2026},
month = sep,
doi = {10.7759/cureus.116849},
url = {https://europepmc.org/article/MED/42927390},
note = {CC BY},
}
RIS
TY - JOUR
TI - Confirmed Myocarditis-Myositis Overlap Without Myasthenia Gravis: Evaluating for Triple M Syndrome Following Combined Enfortumab Vedotin and Pembrolizumab Therapy.
AU - Bryan Ashong
AU - Yash Ranga
PY - 2026
DA - 2026/09/24
JO - Cureus
DO - 10.7759/cureus.116849
UR - https://europepmc.org/article/MED/42927390
AB - 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.
SN - 2168-8184
ER -