Myers G
Department of Pharmacy, Horizon Health Network-The Moncton Hospital, Moncton, NB, and Canadian Association of Pharmacy in Oncology, Vancouver, BC.
Curr Oncol. 2018 Oct;25(5):342-347. doi: 10.3747/co.25.4235. Epub 2018 Oct 31.
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.
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。