Fulminant Myocarditis with Combination Immune Checkpoint Blockade

By Douglas B. Johnson, J. Balko, Margaret L. Compton, S. Chalkias, J. Gorham, Yaomin Xu, Mellissa J. Hicks, I. Puzanov, Matthew R. Alexander, Tyler L Bloomer and 22 more. New England Journal of Medicine, 2016

1,956 citations recorded by the source corpus.

Summary Immune checkpoint inhibitors significantly improve clinical outcomes in numerous malignancies, but high-grade immune-related adverse events can occur, particularly with combination immunotherapy. Herein, we report two melanoma patients who developed fatal myocarditis following treatment with ipilimumab and nivolumab. Both patients developed myositis with rhabdomyolysis, early progressive and refractory cardiac electrical instability, and myocarditis with robust T-cell and macrophage infiltrates. Selective clonal T-cell populations infiltrating the myocardium were identical to those present in tumor and skeletal muscle. Pharmacovigilance data revealed that myocarditis occurred in 0.27% of patients treated with ipilimumab/nivolumab, suggesting this is a rare, potentially fatal, T-cell-driven drug reaction.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/fe6be7d5f0af6d904fdc777ffa8fd382cdae7e9c

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In Molecular Biology

1. J. Wolchok
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Citations in the corpus

• Myocarditis in Patients Treated With Immune Checkpoint Inhibitors (2018, positive): “An ECG is an inexpensive test and widely available, and conduction abnormalities have been reported in the setting of ICI-associated myocarditis (5); however, it lacks sensitivity and specificity for the diagnosis of myocarditis (24).”
• Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis (2018, neutral): “2018 (up to January 15) 3 (2) 30 (9) 15 (17) <.”
• Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update (2021, background): “diminished ejection fraction.(149,192) Conduction abnormalities can include complete heart block.”
• Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline (2018, methodology): “daily) and the possible addition of mycophenolate, infliximab, or ATG.(75,111-113,117) Management of symptoms of arrhythmia and Table 9.”
• Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group (2017, background): “However, myocarditis, pericarditis and cardiac dysfunction due to ICIs are rare and the true incidence is unknown; current estimates suggest less than 1% of patients [22].”