一项关于免疫检查点抑制剂相关心血管不良事件的回顾性分析。
A retrospective analysis of cardiovascular adverse events associated with immune checkpoint inhibitors.
作者信息
Lal Jessica Castrillon, Brown Sherry-Ann, Collier Patrick, Cheng Feixiong
机构信息
Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, 44195, USA.
出版信息
Cardiooncology. 2021 May 28;7(1):19. doi: 10.1186/s40959-021-00106-x.
BACKGROUND
Modern therapies in oncology have increased cancer survivorship, as well as the incidence of cardiovascular adverse events. While immune checkpoint inhibitors have shown significant clinical impact in several cancer types, the incidence of immune-related cardiovascular (CV) adverse events poses an additional health concern and has been reported.
METHODS
We performed a retrospective analysis of the FDA Adverse Event Reporting System data of suspect product reports for immunotherapy and classical chemotherapy from January 2010-March 2020. We identified 90,740 total adverse event reports related to immune checkpoint inhibitors and classical chemotherapy.
RESULTS
We found that myocarditis was significantly associated with patients receiving anti-program cell death protein 1 (PD-1) or anti-program death ligand 1 (PD-L1), odds ratio (OR) = 23.86 (95% confidence interval [CI] 11.76-48.42, (adjusted p-value) q < 0.001), and combination immunotherapy, OR = 7.29 (95% CI 1.03-51.89, q = 0.047). Heart failure was significantly associated in chemotherapy compared to PD-(L)1, OR = 0.50 (95% CI 0.37-0.69, q < 0.001), CTLA4, OR = 0.08 (95% CI 0.03-0.20, q < 0.001), and combination immunotherapy, OR = 0.25 (95% CI 0.13-0.48, q < 0.001). Additionally, we observe a sex-specificity towards males in cardiac adverse reports for arrhythmias, OR = 0.81 (95% CI 0.75-0.87, q < 0.001), coronary artery disease, 0.63 (95% CI 0.53-0.76, q < 0.001), myocardial infarction, OR = 0.60 (95% CI 0.53-0.67, q < 0.001), myocarditis, OR = 0.59 (95% CI 0.47-0.75, q < 0.001) and pericarditis, OR = 0.5 (95% CI 0.35-0.73, q < 0.001).
CONCLUSION
Our study provides the current risk estimates of cardiac adverse events in patients treated with immunotherapy compared to conventional chemotherapy. Understanding the clinical risk factors that predispose immunotherapy-treated cancer patients to often fatal CV adverse events will be crucial in Cardio-Oncology management.
背景
肿瘤学中的现代疗法提高了癌症生存率，同时也增加了心血管不良事件的发生率。虽然免疫检查点抑制剂在多种癌症类型中显示出显著的临床效果，但免疫相关心血管（CV）不良事件的发生率引发了额外的健康担忧，且已有相关报道。
方法
我们对2010年1月至2020年3月期间美国食品药品监督管理局（FDA）不良事件报告系统中免疫疗法和传统化疗的可疑产品报告数据进行了回顾性分析。我们共识别出90740份与免疫检查点抑制剂和传统化疗相关的不良事件报告。
结果
我们发现，心肌炎与接受抗程序性细胞死亡蛋白1（PD - 1）或抗程序性死亡配体1（PD - L1）治疗的患者显著相关，比值比（OR）= 23.86（95%置信区间[CI] 11.76 - 48.42，（校正p值）q < 0.001），与联合免疫疗法也显著相关，OR = 7.29（95% CI 1.03 - 51.89，q = 0.047）。与PD -（L）1相比，心力衰竭在化疗患者中显著相关，OR = 0.50（95% CI 0.37 - 0.69，q < 0.001），与CTLA4相比，OR = 0.08（95% CI 0.03 - 0.20，q < 0.001），与联合免疫疗法相比，OR = 0.25（95% CI 0.13 - 0.48，q < 0.001）。此外，我们观察到在心脏不良事件报告中，男性在心律失常方面存在性别特异性，OR = 0.81（95% CI 0.75 - 0.87，q < 0.001），冠状动脉疾病方面，OR = 0.63（95% CI 0.53 - 0.76，q < 0.001），心肌梗死方面，OR = 0.60（95% CI 0.53 - 0.67，q < 0.001），心肌炎方面，OR = 0.59（95% CI 0.47 - 0.75，q < 0.001），心包炎方面，OR = 0.5（95% CI 0.35 - 0.73，q < 0.001）。
结论
我们的研究提供了与传统化疗相比，接受免疫疗法治疗的患者发生心脏不良事件的当前风险估计。了解使接受免疫疗法治疗的癌症患者易发生往往致命的CV不良事件的临床风险因素，在心脏肿瘤学管理中将至关重要。
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