Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York2Weill Cornell Medical College, New York, New York.
JAMA Oncol. 2016 Oct 1;2(10):1346-1353. doi: 10.1001/jamaoncol.2016.1051.
The development of immune checkpoint inhibitors targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death-1 (PD-1) has significantly improved the treatment of a variety of cancers and led to US Food and Drug Administration approvals for patients with a variety of malignant neoplasms. Immune checkpoint inhibitors enhance antitumor immunity by blocking negative regulators of T-cell function that exist both on immune cells and on tumor cells. Although these agents can lead to remarkable responses, their use can also be associated with unique immune-related adverse effects (irAEs).
In general, use of PD-1 inhibitors such as nivolumab and pembrolizumab has a lower incidence of irAEs compared with those that block CTLA-4 such as ipilimumab. The combination of nivolumab and ipilimumab has a higher rate of irAEs than either approach as monotherapy. Consensus guidelines regarding the treatment of the most common irAEs including rash, colitis, hepatitis, endocrinopathies, and pneumonitis have been established. The mainstay of irAE treatment consists of immunosuppression with corticosteroids or other immunosuppressant agents such as infliximab; most irAEs will resolve with appropriate management.
The clinical use of immune checkpoint inhibitors is expanding rapidly. Oncology practitioners will therefore be required to recognize and manage irAEs in a growing patient population. Early recognition and treatment are essential to prevent patient morbidity and mortality, and adherence to established algorithms is recommended.
针对细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）和程序性细胞死亡蛋白 1（PD-1）的免疫检查点抑制剂的开发极大地改善了多种癌症的治疗效果，并导致美国食品和药物管理局批准了多种恶性肿瘤患者使用这些药物。免疫检查点抑制剂通过阻断存在于免疫细胞和肿瘤细胞上的 T 细胞功能的负调节剂来增强抗肿瘤免疫。尽管这些药物可以导致显著的反应，但它们的使用也可能与独特的免疫相关不良事件（irAEs）相关。
一般来说，与阻断 CTLA-4 的药物（如伊匹单抗）相比，使用 PD-1 抑制剂（如纳武利尤单抗和帕博利珠单抗）的 irAEs 发生率较低。纳武利尤单抗和伊匹单抗联合使用的 irAEs 发生率高于任何一种单药治疗。已经制定了关于最常见的 irAEs（包括皮疹、结肠炎、肝炎、内分泌疾病和肺炎）的治疗共识指南。irAE 治疗的主要方法是使用皮质类固醇或其他免疫抑制剂（如英夫利昔单抗）进行免疫抑制；大多数 irAEs 经适当治疗后会得到缓解。
免疫检查点抑制剂的临床应用正在迅速扩大。因此，肿瘤学从业者将需要在不断增长的患者群体中识别和管理 irAEs。早期识别和治疗对于预防患者的发病率和死亡率至关重要，建议遵循既定的算法。
