Title |
Fulminant Myocarditis with Combination Immune Checkpoint Blockade
|
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Published in |
New England Journal of Medicine, November 2016
|
DOI | 10.1056/nejmoa1609214 |
Pubmed ID | |
Authors |
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 |
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.). |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 102 | 28% |
Spain | 22 | 6% |
United Kingdom | 13 | 4% |
France | 12 | 3% |
Japan | 10 | 3% |
Canada | 10 | 3% |
Australia | 7 | 2% |
Mexico | 4 | 1% |
Turkey | 4 | 1% |
Other | 38 | 10% |
Unknown | 143 | 39% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 217 | 59% |
Scientists | 76 | 21% |
Practitioners (doctors, other healthcare professionals) | 59 | 16% |
Science communicators (journalists, bloggers, editors) | 12 | 3% |
Unknown | 1 | <1% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 3 | <1% |
Korea, Republic of | 2 | <1% |
Sweden | 1 | <1% |
Brazil | 1 | <1% |
Canada | 1 | <1% |
United Kingdom | 1 | <1% |
Unknown | 891 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 166 | 18% |
Other | 94 | 10% |
Student > Ph. D. Student | 78 | 9% |
Student > Doctoral Student | 65 | 7% |
Student > Postgraduate | 61 | 7% |
Other | 194 | 22% |
Unknown | 242 | 27% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 390 | 43% |
Biochemistry, Genetics and Molecular Biology | 56 | 6% |
Agricultural and Biological Sciences | 40 | 4% |
Immunology and Microbiology | 38 | 4% |
Pharmacology, Toxicology and Pharmaceutical Science | 21 | 2% |
Other | 70 | 8% |
Unknown | 285 | 32% |