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Fulminant Myocarditis with Combination Immune Checkpoint Blockade.


ABSTRACT: 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.).

SUBMITTER: Johnson DB 

PROVIDER: S-EPMC5247797 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Fulminant Myocarditis with Combination Immune Checkpoint Blockade.

Johnson Douglas B DB   Balko Justin M JM   Compton Margaret L ML   Chalkias Spyridon S   Gorham Joshua J   Xu Yaomin Y   Hicks Mellissa M   Puzanov Igor I   Alexander Matthew R MR   Bloomer Tyler L TL   Becker Jason R JR   Slosky David A DA   Phillips Elizabeth J EJ   Pilkinton Mark A MA   Craig-Owens Laura L   Kola Nina N   Plautz Gregory G   Reshef Daniel S DS   Deutsch Jonathan S JS   Deering Raquel P RP   Olenchock Benjamin A BA   Lichtman Andrew H AH   Roden Dan M DM   Seidman Christine E CE   Koralnik Igor J IJ   Seidman Jonathan G JG   Hoffman Robert D RD   Taube Janis M JM   Diaz Luis A LA   Anders Robert A RA   Sosman Jeffrey A JA   Moslehi Javid J JJ  

The New England journal of medicine 20161101 18


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 pr  ...[more]

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