Fulminant Myocarditis with Combination Immune Checkpoint Blockade.
Fulminant Myocarditis with Combination Immune Checkpoint Blockade.
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结合免疫检查点封锁的暴发性心肌炎。
DOI：
10.1056/nejmoa1609214
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发表时间：
2016-11-03
期刊：
影响因子：
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通讯作者：
Moslehi JJ
中科院分区：
文献类型：
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作者：
Johnson DB;Balko JM;Compton ML;Chalkias S;Gorham J;Xu Y;Hicks M;Puzanov I;Alexander MR;Bloomer TL;Becker JR;Slosky DA;Phillips EJ;Pilkinton MA;Craig-Owens L;Kola N;Plautz G;Reshef DS;Deutsch JS;Deering RP;Olenchock BA;Lichtman AH;Roden DM;Seidman CE;Koralnik IJ;Seidman JG;Hoffman RD;Taube JM;Diaz LA Jr;Anders RA;Sosman JA;Moslehi JJ
免疫检查点抑制剂显著改善了许多恶性肿瘤的临床结局，但可能发生高度免疫相关的不良事件，特别是联合免疫治疗。在此，我们报告了两名黑色素瘤患者，他们在接受伊匹单抗和纳武单抗治疗后发生了致命性心肌炎。两名患者均发生肌炎伴横纹肌溶解、早期进行性和难治性心脏电不稳定以及心肌炎伴强T细胞和巨噬细胞浸润。浸润心肌的选择性克隆T细胞群与肿瘤和骨骼肌中存在的T细胞群相同。药物警戒数据显示，接受伊匹单抗/纳武单抗治疗的患者中有0.27%发生心肌炎，表明这是一种罕见的、潜在致死性的T细胞驱动的药物反应。
Immune checkpoint inhibitors significantly improve clinical outcomes in numerous malignancies, but high-grade immune-related adverse events can occur, particularly with combination immunotherapy. Herein, we report two melanoma patients who developed fatal myocarditis following treatment with ipilimumab and nivolumab. Both patients developed myositis with rhabdomyolysis, early progressive and refractory cardiac electrical instability, and myocarditis with robust T-cell and macrophage infiltrates. Selective clonal T-cell populations infiltrating the myocardium were identical to those present in tumor and skeletal muscle. Pharmacovigilance data revealed that myocarditis occurred in 0.27% of patients treated with ipilimumab/nivolumab, suggesting this is a rare, potentially fatal, T-cell-driven drug reaction.