TY - JOUR
T1 - Fulminant myocarditis with combination immune checkpoint blockade
AU - Johnson, Douglas B.
AU - Balko, Justin M.
AU - Compton, Margaret L.
AU - Chalkias, Spyridon
AU - Gorham, Joshua
AU - Xu, Yaomin
AU - Hicks, Mellissa
AU - Puzanov, Igor
AU - Alexander, Matthew R.
AU - Bloomer, Tyler L.
AU - Becker, Jason R.
AU - Slosky, David A.
AU - Phillips, Elizabeth J.
AU - Pilkinton, Mark A.
AU - Craig-Owens, Laura
AU - Kola, Nina
AU - Plautz, Gregory
AU - Reshef, Daniel S.
AU - Deutsch, Jonathan S.
AU - Deering, Raquel P.
AU - Olenchock, Benjamin A.
AU - Lichtman, Andrew H.
AU - Roden, Dan M.
AU - Seidman, Christine E.
AU - Koralnik, Igor J.
AU - Seidman, Jonathan G.
AU - Hoffman, Robert D.
AU - Taube, Janis M.
AU - Diaz, Luis A.
AU - Anders, Robert A.
AU - Sosman, Jeffrey A.
AU - Moslehi, Javid J.
N1 - Publisher Copyright:
© 2016 Massachusetts Medical Society.
PY - 2016/11/3
Y1 - 2016/11/3
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84994144982
U2 - 10.1056/NEJMoa1609214
DO - 10.1056/NEJMoa1609214
M3 - Article
C2 - 27806233
AN - SCOPUS:84994144982
SN - 0028-4793
VL - 375
SP - 1749
EP - 1755
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 18
ER -