Kumar Vivek, Chaudhary Neha, Garg Mohit, Floudas Charalampos S, Soni Parita, Chandra Abhinav B
Department of Medicine, Maimonides Medical Center Brooklyn, NY, USA.
Department of Pediatrics, Maimonides Medical Center Brooklyn, NY, USA.
Front Pharmacol. 2017 Feb 8;8:49. doi: 10.3389/fphar.2017.00049. eCollection 2017.
The indications of immune checkpoint inhibitors (ICIs) are set to rise further with the approval of newer agent like atezolimumab for use in patients with advanced stage urothelial carcinoma. More frequent use of ICIs has improved our understanding of their unique side effects, which are known as immune-related adverse events (irAEs). The spectrum of irAEs has expanded beyond more common manifestations such as dermatological, gastrointestinal and endocrine effects to rarer presentations involving nervous, hematopoietic and urinary systems. There are new safety data accumulating on ICIs in patients with previously diagnosed autoimmune conditions. It is challenging for clinicians to continuously update their working knowledge to diagnose and manage these events successfully. If diagnosed timely, the majority of events are completely reversible, and temporary immunosuppression with glucocorticoids, infliximab or other agents is warranted only in the most severe grade illnesses. The same principles of management will possibly apply as newer anti- cytotoxic T lymphocytes-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1/PD-L1) antibodies are introduced. The current focus of research is for prophylaxis and for biomarkers to predict the onset of these toxicities. In this review we summarize the irAEs of ICIs and emphasize their growing spectrum and their management algorithms, to update oncology practitioners.
随着阿替利珠单抗等新型药物获批用于晚期尿路上皮癌患者，免疫检查点抑制剂（ICI）的适应证有望进一步增加。ICI使用频率的提高增进了我们对其独特副作用的了解，这些副作用被称为免疫相关不良事件（irAE）。irAE的范围已从更常见的表现（如皮肤、胃肠道和内分泌影响）扩展到涉及神经、造血和泌尿系统的罕见表现。在先前诊断为自身免疫性疾病的患者中，关于ICI的新安全性数据不断积累。临床医生要不断更新专业知识以成功诊断和处理这些事件具有挑战性。如果及时诊断，大多数事件是完全可逆的，仅在最严重的等级疾病中才需要用糖皮质激素、英夫利昔单抗或其他药物进行临时免疫抑制。随着新型抗细胞毒性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/PD-L1）抗体的引入，相同的管理原则可能适用。当前的研究重点是预防和预测这些毒性发作的生物标志物。在本综述中，我们总结了ICI的irAE，并强调其不断扩大的范围及其管理算法，以更新肿瘤学从业者的知识。
