Fulminant Myocarditis with Combination Immune Checkpoint Blockade

被引：1773

作者：

Johnson, Douglas B. dbj ^{[1
]}

Balko, Justin M. jmb ^{[1
,2
,8
]}

Compton, Margaret L. mlc ^{[3
]}

Chalkias, Spyridon sc ^{[10
,11
]}

Gorham, Joshua jc ^{[14
]}

Xu, Yaomin yx ^{[4
,6
,9
]}

Hicks, Mellissa mh ^{[1
]}

Puzanov, Igor ip ^{[1
]}

Alexander, Matthew R. mra ^{[1
]}

Bloomer, Tyler L. tlb ^{[1
]}

Becker, Jason R. jrb ^{[1
]}

Slosky, David A. das ^{[1
,7
]}

Phillips, Elizabeth J. ejp ^{[1
]}

Pilkinton, Mark A. map ^{[1
]}

Craig-Owens, Laura lco ^{[3
]}

Kola, Nina nk ^{[16
]}

Plautz, Gregory gp ^{[16
]}

Reshef, Daniel S. dsr ^{[16
]}

Deutsch, Jonathan S. jsd ^{[16
]}

Deering, Raquel P. rpd ^{[17
]}

Olenchock, Benjamin A. bao ^{[12
]}

Lichtman, Andrew H. ahl ^{[13
]}

Roden, Dan M. dmr ^{[1
,5
,6
]}

Seidman, Christine E. ces ^{[12
,14
,15
]}

Koralnik, Igor J. ijk ^{[11
]}

Seidman, Jonathan G. jgs ^{[12
,14
]}

Hoffman, Robert D. rdh ^{[3
]}

Taube, Janis M. jmt ^{[18
,19
]}

Diaz, Luis A. Jr lad ^{[20
]}

Anders, Robert A. raa ^{[18
]}

Sosman, Jeffrey A. jas ^{[1
]}

Moslehi, Javid J. jjm ^{[1
,2
,7
]}

机构：

[1] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA

[2] Vanderbilt Univ, Med Ctr, Dept Canc Biol, Nashville, TN USA

[3] Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Nashville, TN USA

[4] Vanderbilt Univ, Med Ctr, Dept Biostat, Nashville, TN USA

[5] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA

[6] Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN 37232 USA

[7] Vanderbilt Univ, Med Ctr, Cardiooncol Program, 2220 Pierce Ave, Nashville, TN 37232 USA

[8] Vanderbilt Univ, Med Ctr, Breast Canc Res Program, Nashville, TN 37232 USA

[9] Vanderbilt Univ, Med Ctr, Ctr Quantitat Sci, Nashville, TN 37232 USA

[10] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA

[11] Beth Israel Deaconess Med Ctr, Div Neuroimmunol, Boston, MA 02215 USA

[12] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA

[13] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA

[14] Harvard Med Sch, Dept Genet, Boston, MA USA

[15] Howard Hughes Med Inst, Chevy Chase, MD USA

[16] Bristol Myers Squibb, New York, NY USA

[17] Neon Therapeut, Cambridge, MA USA

[18] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA

[19] Johns Hopkins Univ, Dept Dermatol, Baltimore, MD 21218 USA

[20] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2016年 / 375卷 / 18期

基金：

美国国家卫生研究院;

关键词：

DILATED CARDIOMYOPATHY; UNTREATED MELANOMA; PD-1; BLOCKADE; IPILIMUMAB; NIVOLUMAB; PEMBROLIZUMAB; INFLAMMATION; AUTOPSY; HEART; RISK;

D O I：

10.1056/NEJMoa1609214

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.)

引用

页码：1749 / 1755

页数：7

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