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本文引用的文献

1
Safety of Programmed Death-1 Pathway Inhibitors Among Patients With Non-Small-Cell Lung Cancer and Preexisting Autoimmune Disorders.程序性死亡-1 通路抑制剂在患有非小细胞肺癌和既往自身免疫性疾病患者中的安全性。
J Clin Oncol. 2018 Jul 1;36(19):1905-1912. doi: 10.1200/JCO.2017.77.0305. Epub 2018 May 10.
2
Immune Checkpoint Inhibitor Therapy in Patients With Autoimmune Disease.自身免疫性疾病患者的免疫检查点抑制剂治疗
Oncology (Williston Park). 2018 Apr 15;32(4):190-4.
3
Clinical assessment of immune-related adverse events.免疫相关不良事件的临床评估
Ther Adv Med Oncol. 2018 Mar 30;10:1758835918764628. doi: 10.1177/1758835918764628. eCollection 2018.
4
Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: systematic review and meta-analysis.抗PD-1和抗PD-L1药物的免疫相关不良事件:系统评价与荟萃分析
BMJ. 2018 Mar 14;360:k793. doi: 10.1136/bmj.k793.
5
Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline.免疫检查点抑制剂治疗患者免疫相关不良反应的管理:美国临床肿瘤学会临床实践指南。
J Clin Oncol. 2018 Jun 10;36(17):1714-1768. doi: 10.1200/JCO.2017.77.6385. Epub 2018 Feb 14.
6
Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations.PD-1 和 PD-L1 抑制剂作为癌症免疫疗法的一种形式的发展:注册试验的综合回顾和未来的考虑。
J Immunother Cancer. 2018 Jan 23;6(1):8. doi: 10.1186/s40425-018-0316-z.
7
Immune-Related Adverse Events Associated with Immune Checkpoint Blockade.与免疫检查点阻断相关的免疫相关不良事件。
N Engl J Med. 2018 Jan 11;378(2):158-168. doi: 10.1056/NEJMra1703481.
8
Use of Immune Checkpoint Inhibitors in the Treatment of Patients With Cancer and Preexisting Autoimmune Disease: A Systematic Review.免疫检查点抑制剂在治疗合并自身免疫性疾病的癌症患者中的应用:系统评价。
Ann Intern Med. 2018 Jan 16;168(2):121-130. doi: 10.7326/M17-2073. Epub 2018 Jan 2.
9
Dermatologic Reactions to Immune Checkpoint Inhibitors : Skin Toxicities and Immunotherapy.免疫检查点抑制剂的皮肤不良反应:皮肤毒性与免疫治疗
Am J Clin Dermatol. 2018 Jun;19(3):345-361. doi: 10.1007/s40257-017-0336-3.
10
Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group.管理免疫检查点抑制剂相关毒性:癌症免疫治疗学会(SITC)毒性管理工作组的共识建议。
J Immunother Cancer. 2017 Nov 21;5(1):95. doi: 10.1186/s40425-017-0300-z.

免疫检查点抑制剂的免疫相关不良事件:简要综述。

Immune-related adverse events of immune checkpoint inhibitors: a brief review.

作者信息

Myers G

机构信息

Department of Pharmacy, Horizon Health Network-The Moncton Hospital, Moncton, NB, and Canadian Association of Pharmacy in Oncology, Vancouver, BC.

出版信息

Curr Oncol. 2018 Oct;25(5):342-347. doi: 10.3747/co.25.4235. Epub 2018 Oct 31.

DOI:10.3747/co.25.4235
PMID:30464684
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6209551/
Abstract

Immune checkpoint inhibitors (icis) such as inhibitors of ctla-4, PD-1, and PD-L1, given as monotherapy or combination therapy have emerged as effective treatment options for immune-sensitive solid tumours and hematologic malignancies. The benefits of icis can be offset by immune-related adverse events (iraes) that leave all organ systems vulnerable and subsequently increase the risk for morbidity and mortality. Because of fluctuating onset and prolonged duration, the toxicities associated with iraes represent a shift from the understanding of conventional anticancer toxicities. The ctla-4 and PD-1/PD-L1 inhibitors modulate T-cell response differently, resulting in distinct toxicity patterns, toxicity kinetics, and dose-toxicity relationships. Using individualized patient education, screening, and assessment for the early identification of iraes is key to proactive management and is therefore key to improving outcomes and prolonging therapy. Management of iraes is guided by appropriate grading, which sets the stage for the treatment setting (outpatient vs. inpatient), ici treatment course (delay vs. discontinuation), supportive care, corticosteroid use, organ specialist consultation, and additional immunosuppression. Health care professionals in oncology must work collaboratively with emergency and community colleagues to facilitate an understanding of iraes in an effort to optimize seamless care.

摘要

免疫检查点抑制剂(ICIs),如CTLA-4、PD-1和PD-L1的抑制剂,作为单一疗法或联合疗法,已成为免疫敏感实体瘤和血液系统恶性肿瘤的有效治疗选择。ICIs的益处可能会被免疫相关不良事件(irAEs)抵消,这些不良事件会使所有器官系统变得脆弱,进而增加发病和死亡风险。由于发病时间波动且持续时间较长,与irAEs相关的毒性代表了对传统抗癌毒性理解的转变。CTLA-4和PD-1/PD-L1抑制剂对T细胞反应的调节方式不同,导致不同的毒性模式、毒性动力学和剂量-毒性关系。通过个性化的患者教育、筛查和评估来早期识别irAEs是积极管理的关键,因此也是改善治疗效果和延长治疗时间的关键。irAEs的管理以适当的分级为指导,这为治疗环境(门诊与住院)、ICI治疗过程(延迟与停药)、支持性护理、皮质类固醇的使用、器官专科会诊和额外的免疫抑制奠定了基础。肿瘤学领域的医疗保健专业人员必须与急诊科和社区的同事合作,以促进对irAEs的了解,努力优化无缝护理。