Immune Checkpoint Inhibitors-Associated Cardiotoxicity.
Immune Checkpoint Inhibitors-Associated Cardiotoxicity.
复制标题
免疫检查点抑制剂相关的神经毒性。
DOI：
10.3390/cancers14051145
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发表时间：
2022-02-23
期刊：
影响因子：
5.2
通讯作者：
Ying J
中科院分区：
文献类型：
--
作者：
Li C;Bhatti SA;Ying J
随着免疫系统的非特异性激活，免疫检查点抑制剂 (ICIs) 可能会导致每个器官系统出现脱靶免疫相关不良事件 (irAE)。免疫相关的心脏毒性很少见，但通常是致命的。针对不同癌症类型和药物与 ICI 相关的心脏毒性进行的大规模人群研究是有限的。利用来自大型医疗保健组织网络的数据，本研究旨在：(1) 提供 ICI 相关心脏毒性发生率的估计，(2) 确定与发生 ICI 相关心脏毒性风险相关的患者和临床特征，以及 (3) 评估与使用 ICI 后未发生心脏毒性的患者相比，经历 ICI 相关心脏毒性的患者的总体生存率。基于人群的大型研究检查了不同癌症类型和药物之间 ICI 相关心脏毒性的差异。从大型医疗保健组织网络中提取了 5518 名接受至少一个周期 ICI 的癌症患者的数据。 ICI 治疗组按第一种 ICI 药物（ipilimumab、nivolumab、pembrolizumab、cemiplimab、avelumab、atezolizumab 或 durvalumab）或其类别（PD-1 抑制剂、PD-L1 抑制剂、CTLA4 抑制剂或其组合（ipilimumab + nivolumab））进行分类。使用调整 ICI 治疗组、患者人口统计和临床特征以及癌症部位的竞争风险回归模型，分析 ICI 启动后一年内发生的首次心脏不良事件 (CAE)（心律失常、急性心肌梗死、心肌炎、心肌病或心包炎）的时间。到第 12 个月，12.5% 的人出现心脏毒性。最常见的心脏毒性是心律失常（9.3%），2.1% 发展为心肌炎。调整患者特征和癌症部位后，开始接受伊匹单抗（调整后风险比 (aHR)：2.00；95% CI：1.49–2.70；p < 0.001）或派姆单抗（aHR：1.21；95% CI：1.01–1.46；p = 0.040）单药治疗的患者在一个疗程内发生 CAE 的风险较高。与纳武单抗单一疗法相比。与其他药物相比，伊匹单抗和派姆单抗的使用可能会增加心脏毒性的风险。与纳武单抗和其他 PD-L1 药物相比，Avelumab 还估计风险高度升高（aHR：1.92；95% CI：0.85-4.34；p = 0.117），尽管该估计未达到统计学显着性，值得未来研究。
With nonspecific activation of the immune system, immune checkpoint inhibitors (ICIs) can lead to off-target immune-related adverse events (irAEs) to every organ system. Immune-related cardiotoxicity is rare but often fatal. Large population-based studies examining different ICI-associated cardiotoxicity across cancer types and agents are limited. Using data from a large network of health care organizations, this study aims to: (1) provide an estimate of the incidence of ICI-associated cardiotoxicity, (2) to determine patient and clinical characteristics associated with the risk of developing ICI-associated cardiotoxicity, and (3) to assess the overall survival of patients experiencing ICI-associated cardiotoxicity compared to patients who did not develop cardiotoxicity after ICI use. Large population-based studies examining differences in ICI-associated cardiotoxicity across cancer types and agents are limited. Data of 5518 cancer patients who received at least one cycle of ICIs were extracted from a large network of health care organizations. ICI treatment groups were classified by the first ICI agent(s) (ipilimumab, nivolumab, pembrolizumab, cemiplimab, avelumab, atezolizumab, or durvalumab) or its class (PD-1 inhibitors, PD-L1 inhibitors, CTLA4-inhibitors, or their combination (ipilimumab + nivolumab)). Time to first cardiac adverse event (CAE) (arrhythmia, acute myocardial infarction, myocarditis, cardiomyopathy, or pericarditis) developed within one year after ICI initiation was analyzed using a competing-risks regression model adjusting for ICI treatment groups, patient demographic and clinical characteristics, and cancer sites. By month 12, 12.5% developed cardiotoxicity. The most common cardiotoxicity was arrhythmia (9.3%) and 2.1% developed myocarditis. After adjusting for patient characteristics and cancer sites, patients who initiated on monotherapy with ipilimumab (adjusted Hazard Ratio (aHR): 2.00; 95% CI: 1.49–2.70; p < 0.001) or pembrolizumab (aHR: 1.21; 95% CI: 1.01–1.46; p = 0.040) had a higher risk of developing CAEs within one year compared to nivolumab monotherapy. Ipilimumab and pembrolizumab use may increase the risk of cardiotoxicity compared to other agents. Avelumab also estimated a highly elevated risk (aHR: 1.92; 95% CI: 0.85–4.34; p = 0.117) compared to nivolumab and other PD-L1 agents, although the estimate did not reach statistical significance, warranting future studies.
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
19.6
作者：
Cortazar FB;Marrone KA;Troxell ML;Ralto KM;Hoenig MP;Brahmer JR;Le DT;Lipson EJ;Glezerman IG;Wolchok J;Cornell LD;Feldman P;Stokes MB;Zapata SA;Hodi FS;Ott PA;Yamashita M;Leaf DE
通讯作者：
Leaf DE
影响因子：
37.8
作者：
Bonaca, Marc P.;Olenchock, Benjamin A.;Moslehi, Javid
通讯作者：
Moslehi, Javid
影响因子：
7.2
作者：
Davies M;Duffield EA
通讯作者：
Duffield EA
影响因子：
5.2
作者：
Deshpande RP;Sharma S;Watabe K
通讯作者：
Watabe K