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. DeeringBenjamin 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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1765 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1749-1755
Number of pages7
JournalNew England Journal of Medicine
Volume375
Issue number18
DOIs
StatePublished - Nov 3 2016

Funding

Supported by funding from the Bready Family Foundation (to Drs. Johnson and Balko), the National Cancer Institute (grant 6R00CA181491, to Dr. Balko), the Vanderbilt-Ingram Cancer Center Ambassadors (to Drs. Balko and Moslehi), the Breast Cancer Specialized Program of Research Excellence (grant P50 CA098131, to Drs. Balko and Moslehi), the National Comprehensive Cancer Network Young Investigator Award (to Dr. Johnson), the National Institutes of Health (grant K08 HL119355, to Dr. Olenchock; grant P50 GM115305, to Drs. Phillips and Roden; and grants U01-HL098188, U01-HL098147, U01-HL098153, U01- HL098163, U01-HL098123, and U01-HL098162, to Dr. J. Seidman), the Howard Hughes Medical Institute (to Dr. C. Seidman), and Gilead Life Sciences (to Dr. Olenchock).

ASJC Scopus subject areas

  • General Medicine

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