SHM Converge Scientific Abstract ePoster Gallery-Triple Threat Toxicity: A Case of Pembrolizumab-Induced Triple M Overlap Syndrome

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This case report describes a rare and severe immune-related adverse event from pembrolizumab, known as Triple M Overlap Syndrome (TMOS), which includes myocarditis, myositis, and myasthenia gravis. The patient was a 75-year-old man with advanced urothelial carcinoma receiving enfortumab vedotin and pembrolizumab who developed progressively worsening muscle weakness, ptosis, dyspnea on exertion, and edema over two weeks.<br /><br />On examination, he had fatigable weakness, bilateral ptosis, diminished reflexes, and signs of respiratory compromise. Workup showed marked elevation of creatine kinase, troponin T, and NT-proBNP, along with ECG changes and cardiac MRI findings consistent with myocarditis. Muscle biopsy demonstrated necrotizing myopathy. Although testing for myasthenia gravis was nondiagnostic and antibody studies were negative, the overall clinical picture supported TMOS.<br /><br />Initial treatment with high-dose methylprednisolone, pyridostigmine, and IVIG produced minimal improvement, and the patient required BiPAP for respiratory depression. Additional immunosuppression with abatacept led to mild improvement, and later ruxolitinib was associated with reduction in cardiac biomarkers and clinical recovery. He was eventually discharged after dose optimization and multidisciplinary management.<br /><br />The authors emphasize that immune checkpoint inhibitors can cause diverse autoimmune toxicities, and TMOS is particularly dangerous because of its high reported in-hospital mortality of 40–60%. They stress the importance of prompt recognition of the myocarditis-myositis-myasthenia triad whenever any one component is suspected, along with aggressive immunosuppression and close respiratory monitoring to prevent respiratory failure. Hospitalists play a key role in early detection and coordination of care.

Asset Subtitle

Tram T. Tran

Meta Tag

Author List Cristina Alvarez, Lucy Z. Shi, Mamta Parikh, Tram T. Tran, Xiya Wu

Category Clinical Vignettes

Concept Immune-Related Adverse Event

Concept Triple M Overlap Syndrome

Concept Immune Checkpoint Inhibitor

Concept Myocarditis

Concept Myositis

Distinguished Non-Finalist

Presenter Organization University of California Davis

Presenting Author Tram T. Tran

Track Adult

Keywords

pembrolizumab

Triple M Overlap Syndrome

myocarditis

myositis

myasthenia gravis

immune-related adverse event

urothelial carcinoma

creatine kinase

cardiac MRI

immunosuppression

Immune-Related Adverse Event

Triple M Overlap Syndrome

Immune Checkpoint Inhibitor

Myocarditis

Myositis