Department of Medicine, Baystate Medical Center, University of Massachusetts, Springfield, MA, 01103, USA.
Department of Hematology/Oncology, MD Anderson Cancer Center, University of Texas, Houston, TX, USA.
J Cancer Res Clin Oncol. 2019 Jun;145(6):1527-1557. doi: 10.1007/s00432-019-02927-x. Epub 2019 Apr 26.
The advent of immune checkpoint inhibitors in the treatment of certain types of cancers has revolutionized cancer therapy. In general, these novel agents are more tolerable and have better safety profiles than conventional chemotherapy agents. Although a low incidence of myocarditis was noted as a side effect of immune checkpoint inhibitors in clinical trials, it is being increasingly cited in the literature as their use also increases.
Using a combination of search terms in the PubMed/Medline database and manual searches on Google Scholar and the bibliographies of articles identified, we reviewed all cases reported in the English language citing myocarditis associated with either pembrolizumab, nivolumab, ipilimumab, or any combination of these agents.
A total of 42 cases were included in the study. Mean age was 65.5 years; 64% were male, 36% were female. One or two doses preceded the onset of myocarditis in 33% and 29% of cases, respectively. Steroids were used as the first-line therapy in 90% of cases. Complete heart block occurred in 36% of cases. Fourteen (33%) deaths were reported, with 64% and 29% of deaths occurring after one or two doses, respectively.
Most cases and fatalities of myocarditis occurred shortly after initiation of immune checkpoint inhibitor therapy. Arrhythmias, particularly complete heart block, appear to be related to the occurrence of more severe and fatal cases. The use of serial electrocardiograms or biomarkers of myocardial injury may be crucial in detecting early stages of the disease process. Further research establishing more specific guidelines is necessary in dealing with this potentially fatal side effect.
免疫检查点抑制剂在某些类型癌症的治疗中的出现彻底改变了癌症治疗。一般来说，这些新型药物比传统化疗药物更耐受，安全性更好。虽然临床试验中注意到免疫检查点抑制剂的一个副作用是心肌炎发生率低，但随着其使用的增加，它在文献中被越来越多地引用。
我们使用 PubMed/Medline 数据库中的组合搜索词和在 Google Scholar 上的手动搜索以及已确定文章的参考文献，回顾了所有以英语报告的与 pembrolizumab、nivolumab、ipilimumab 或这些药物的任何组合相关的心肌炎病例。
共有 42 例病例纳入研究。平均年龄为 65.5 岁；64%为男性，36%为女性。分别有 33%和 29%的病例在心肌炎发作前使用了 1 或 2 剂药物。90%的病例使用了类固醇作为一线治疗。36%的病例发生完全性心脏传导阻滞。报告了 14 例（33%）死亡，分别有 64%和 29%的死亡发生在使用 1 或 2 剂药物后。
大多数心肌炎病例和死亡发生在免疫检查点抑制剂治疗开始后不久。心律失常，特别是完全性心脏传导阻滞，似乎与更严重和致命病例的发生有关。使用连续心电图或心肌损伤的生物标志物可能对检测疾病过程的早期阶段至关重要。需要进一步的研究来制定更具体的指南，以应对这种潜在的致命副作用。
