Current Diagnosis and Management of Immune Related Adverse Events (irAEs) Induced by Immune Checkpoint Inhibitor Therapy.
Current Diagnosis and Management of Immune Related Adverse Events (irAEs) Induced by Immune Checkpoint Inhibitor Therapy.
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DOI：
10.3389/fphar.2017.00049
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发表时间：
2017
影响因子：
5.6
通讯作者：
Chandra AB
中科院分区：
文献类型：
--
作者：
Kumar V;Chaudhary N;Garg M;Floudas CS;Soni P;Chandra AB
随着atezolimumab等新药物被批准用于晚期尿路上皮癌患者，免疫检查点抑制剂（ICIs）的适应症将进一步增加。更频繁地使用ICIs提高了我们对其独特副作用的理解，这些副作用被称为免疫相关不良事件（irAEs）。irAEs的范围已经从皮肤、胃肠道和内分泌等更常见的表现扩展到涉及神经、造血和泌尿系统的罕见表现。关于先前诊断为自身免疫性疾病的患者使用ICIs的新安全性数据不断积累。对于临床医生来说，不断更新他们的工作知识以成功地诊断和管理这些事件是具有挑战性的。如果诊断及时，大多数事件是完全可逆的，只有在最严重的疾病中，糖皮质激素、英夫利昔单抗或其他药物才能暂时抑制免疫。随着新的抗细胞毒性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，同样的管理原则可能适用。目前的研究重点是预防和生物标志物来预测这些毒性的发生。在这篇综述中，我们总结了ICIs的irae，并强调其不断增长的频谱和管理算法，以更新肿瘤学从业者。
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.