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抗 PD-1 和抗 PD-L1 免疫疗法的冠状动脉毒性:病例报告及文献和国际注册研究综述。

Coronary Toxicities of Anti-PD-1 and Anti-PD-L1 Immunotherapies: a Case Report and Review of the Literature and International Registries.

机构信息

Department of Pneumology and Respiratory Functional Exploration, University Hospital of Tours, Tours, France.

, Impasse du Clos Simon, Building A, Apartment 36, 37520, La Riche, France.

出版信息

Target Oncol. 2018 Aug;13(4):509-515. doi: 10.1007/s11523-018-0579-9.

Abstract

Immunotherapy medications that target programmed death 1 protein (PD-1) and programmed death-ligand 1 (PD-L1), such as nivolumab, pembrolizumab, and atezolizumab, are currently used in the first- or second-line treatment of non-small cell lung cancers, among other indications. However, these agents are associated with immune-related side effects, the most common of which are endocrinopathies, colitis, hepatitis, and interstitial pneumonitis. In contrast, coronary toxicities are rarely reported and remain poorly understood. Here, we describe the case of a patient who developed an acute coronary syndrome when treated with nivolumab as second-line therapy for metastatic pulmonary adenocarcinoma. A review of the literature, the French pharmacovigilance registry, and the World Health Organization pharmacovigilance database led to the identification of four cases of patients with coronary manifestations attributable to anti-PD1 immunotherapy (with no reported cases of patients undergoing anti-PD-L1 immunotherapy), which we describe herein. The potential mechanisms causing adverse coronary reactions to this type of therapy, which is used to treat lung cancer as well as other solid and hematological neoplastic diseases, are also discussed.

摘要

免疫疗法药物,如 nivolumab、pembrolizumab 和 atezolizumab,靶向程序性死亡蛋白 1(PD-1)和程序性死亡配体 1(PD-L1),目前被用于非小细胞肺癌的一线或二线治疗,以及其他适应证。然而,这些药物与免疫相关的副作用相关,最常见的是内分泌疾病、结肠炎、肝炎和间质性肺炎。相比之下,冠状动脉毒性很少报道,且了解甚少。在这里,我们描述了一例转移性肺腺癌患者在接受 nivolumab 二线治疗时发生急性冠状动脉综合征的病例。通过对文献、法国药物警戒登记处和世界卫生组织药物警戒数据库的审查,确定了四起归因于抗 PD-1 免疫治疗的患者出现冠状动脉表现的病例(没有报告接受抗 PD-L1 免疫治疗的患者病例),我们在此描述了这些病例。还讨论了导致这种类型的治疗(用于治疗肺癌以及其他实体瘤和血液系统肿瘤疾病)发生不良冠状动脉反应的潜在机制。

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