Nizam Amanda, Rader Ryan K, Tzeng Alice, Wei Wei, Sheng Iris Yeong-Fung, Martin Allison, Wee Christopher E, Gilligan Timothy D, Gupta Shilpa, Ornstein Moshe C
Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
Department of Medicine, Duke University, Durham, NC.
Clin Genitourin Cancer. 2024 Apr;22(2):368-379. doi: 10.1016/j.clgc.2023.12.007. Epub 2023 Dec 15.
As most patients with metastatic urothelial carcinoma (mUC) will be treated with immune checkpoint inhibitors (ICI), familiarity with their associated immune-related adverse events (irAEs) is critical. We describe the characteristics and outcomes of ICI-treated mUC patients who experienced irAEs requiring treatment interruption (TI) or permanent discontinuation.
ICI-treated mUC patients who developed grade ≥2 irAEs were reviewed. Clinical-, treatment-, and toxicity-related data were evaluated. Toxicity was graded per common terminology for categorization of adverse events v5.0. Cohorts were divided into patients who underwent ICI rechallenge and those who required permanent ICI discontinuation. Time to treatment interruption (TTI), time to next treatment, and duration of clinical benefit were assessed descriptively. Progression-free survival and overall survival (OS) were estimated using Kaplan-Meier methodology.
Of 200 ICI-treated mUC patients at Cleveland Clinic between October 2015 and October 2020, 16 (8%) experienced ≥ grade 2 irAEs necessitating TI. Median TTI among all patients was 6.5 months (range, 1-19). Eleven patients (69%) required corticosteroids. ICI were held and rechallenged in 10 patients (62%) and permanently discontinued in 6 patients (38%). Of the 10 ICI-rechallenged patients, 7 (70%) experienced another irAE upon rechallenge with median time to irAE recurrence of 2.9 months (range, 0.1-10.9); 3 (30%) eventually discontinued ICI due to recrudescent irAEs. Four (40%) of the 10 ICI-rechallenged patients received subsequent therapy. Five (83%) of the 6 patients who permanently discontinued ICI demonstrated durable clinical benefit off therapy with median duration of clinical benefit 17.7 months (range, 14.2-55.2). Two-year OS was 40% (95% CI: 19%-86%) in the ICI rechallenge cohort and 67% (95% CI: 38%-100%) in the permanent discontinuation cohort.
ICI-treated mUC patients who developed irAEs requiring TI had a high rate of subsequent irAEs upon ICI rechallenge. Importantly, patients who permanently discontinued ICI due to irAE demonstrated durable clinical benefit off treatment.
由于大多数转移性尿路上皮癌（mUC）患者将接受免疫检查点抑制剂（ICI）治疗，熟悉其相关的免疫相关不良事件（irAE）至关重要。我们描述了经历需要治疗中断（TI）或永久停药的irAE的ICI治疗的mUC患者的特征和结局。
回顾接受ICI治疗且发生≥2级irAE的mUC患者。评估临床、治疗和毒性相关数据。毒性根据不良事件分类的通用术语标准v5.0进行分级。队列分为接受ICI再挑战的患者和需要永久停用ICI的患者。对治疗中断时间（TTI）、下次治疗时间和临床获益持续时间进行描述性评估。使用Kaplan-Meier方法估计无进展生存期和总生存期（OS）。
在2015年10月至2020年10月期间于克利夫兰诊所接受ICI治疗的200例mUC患者中，16例（8%）发生≥2级irAE，需要TI。所有患者的中位TTI为6.5个月（范围1-19个月）。11例患者（69%）需要使用皮质类固醇。10例患者（62%）暂停ICI并进行再挑战，6例患者（38%）永久停药。在10例接受ICI再挑战的患者中，7例（70%）再挑战时出现另一次irAE，irAE复发的中位时间为2.9个月（范围0.1-10.9个月）；3例（30%）最终因irAE复发而停用ICI。10例接受ICI再挑战的患者中有4例（40%）接受了后续治疗。6例永久停用ICI的患者中有5例（83%）在停药后显示出持久的临床获益，临床获益的中位持续时间为17.7个月（范围14.
