JOURNAL ARTICLE

Fulminant Myocarditis with Combination Immune Checkpoint Blockade

Douglas B Johnson, Justin M Balko, Margaret L Compton, Spyridon Chalkias, Joshua Gorham, Yaomin Xu, Mellissa Hicks, Igor Puzanov, Matthew R Alexander, Tyler L Bloomer, Jason R Becker, David A Slosky, Elizabeth J Phillips, Mark A Pilkinton, Laura Craig-Owens, Nina Kola, Gregory Plautz, Daniel S Reshef, Jonathan S Deutsch, Raquel P Deering, Benjamin A Olenchock, Andrew H Lichtman, Dan M Roden, Christine E Seidman, Igor J Koralnik, Jonathan G Seidman, Robert D Hoffman, Janis M Taube, Luis A Diaz, Robert A Anders, Jeffrey A Sosman, Javid J Moslehi
New England Journal of Medicine 2016 November 3, 375 (18): 1749-1755
27806233
Immune checkpoint inhibitors have improved clinical outcomes associated with numerous cancers, but high-grade, immune-related adverse events can occur, particularly with combination immunotherapy. We report the cases of two patients with melanoma in whom fatal myocarditis developed after treatment with ipilimumab and nivolumab. In both patients, there was development of myositis with rhabdomyolysis, early progressive and refractory cardiac electrical instability, and myocarditis with a robust presence of T-cell and macrophage infiltrates. Selective clonal T-cell populations infiltrating the myocardium were identical to those present in tumors and skeletal muscle. Pharmacovigilance studies show that myocarditis occurred in 0.27% of patients treated with a combination of ipilimumab and nivolumab, which suggests that our patients were having a rare, potentially fatal, T-cell-driven drug reaction. (Funded by Vanderbilt-Ingram Cancer Center Ambassadors and others.).

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