National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio, USA.
J Immunother Cancer. 2021 Jul;9(7). doi: 10.1136/jitc-2020-002119.
Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors can cause unique immune-related adverse effects due to non-specific immunological activation. However, less is known about adverse effects of these drugs in the eye.
Two adverse event databases were retrospectively reviewed. The two databases consisted of a routine adverse event database and a serious adverse event database of expeditiously submitted reports. Patients with any malignancy who had ocular adverse events while on PD-1/PD-L1 inhibitor treatment were included. Patients received nivolumab, pembrolizumab, atezolizumab or durvalumab alone or in combination with other anticancer agents per each trial's protocol. Databases were queried up to May 19, 2020.
In the routine adverse event database, 272 adverse events from 213 patients were reported and in the serious adverse event reporting database, 59 ocular adverse events from 47 patients were reported. A lower estimate of the prevalance from the routine adverse event database showed 259/7727 patients on study treatment arms reporting ocular adverse events (3.3% prevalence). Excluding trials that do not report lower grade adverse events to the routine adverse event database results in a higher end estimate of 242/3255 patients on study treatment arms reporting ocular adverse events (7.4% prevalence). Ocular events occurred early after drug initiation (routine database: median 6 weeks, IQR 0-16, serious adverse events database: median 11 weeks, IQR 6-21). The median Common Terminology Criteria for Adverse Events grade was grade 1 (mild) (IQR 1-2) and grade 2 (moderate) (IQR 2-3) for the routine database and the serious adverse events database, respectively. In-depth analysis of the serious adverse event reports revealed varying degrees of clinical workup, with 30/47 patients (64%) receiving ophthalmological evaluation and 16/47 (34%) of patients having to delay or discontinue treatment. However, 16/47 (34%) patients experienced resolution and 14/47 (30%) patients experienced at least some improvement.
This is one of the largest analyses of ocular adverse events in patients treated with PD-1/PD-L1 inhibitors in the USA. We found ocular adverse events are rare complications of PD-1/PD-L1 inhibitor therapy, can be severe enough to cause treatment discontinuation/delay, and may not always be appropriately evaluated by eye specialists. Standardized plans for ophthalmology evaluation and management of ocular toxicities are needed in studies of patients treated with PD-1/PD-L1 inhibitors.
程序性死亡受体-1（PD-1）和程序性死亡配体 1（PD-L1）抑制剂可因非特异性免疫激活而导致独特的免疫相关不良反应。然而，人们对这些药物在眼部的不良反应知之甚少。
回顾性分析了两个不良事件数据库。这两个数据库包括常规不良事件数据库和快速提交报告的严重不良事件数据库。纳入了在接受 PD-1/PD-L1 抑制剂治疗时出现眼部不良事件的任何恶性肿瘤患者。患者根据每个试验的方案接受纳武单抗、帕博利珠单抗、阿替利珠单抗或度伐利尤单抗单药或联合其他抗癌药物治疗。截至 2020 年 5 月 19 日，对数据库进行了查询。
在常规不良事件数据库中，报告了 213 例患者的 272 例不良事件，在严重不良事件报告数据库中，报告了 47 例患者的 59 例眼部不良事件。常规不良事件数据库中较低的患病率估计显示，在研究治疗臂中，259/7727 例患者报告眼部不良事件（患病率为 3.3%）。排除常规不良事件数据库未报告低级别不良事件的试验，结果为在研究治疗臂中，242/3255 例患者报告眼部不良事件（患病率为 7.4%）。眼部事件在药物起始后早期发生（常规数据库：中位时间 6 周，IQR 0-16；严重不良事件数据库：中位时间 11 周，IQR 6-21）。常规数据库和严重不良事件数据库中，中位不良事件通用术语标准分级均为 1 级（轻度）（IQR 1-2）和 2 级（中度）（IQR 2-3）。对严重不良事件报告的深入分析显示，进行了不同程度的临床检查，30/47 例患者（64%）接受了眼科评估，16/47 例患者（34%）需要延迟或停止治疗。然而，16/47 例患者（34%）得到缓解，14/47 例患者（30%）有一定程度的改善。
这是美国最大规模的分析 PD-1/PD-L1 抑制剂治疗患者眼部不良事件的研究之一。我们发现，眼部不良事件是 PD-1/PD-L1 抑制剂治疗的罕见并发症，严重程度足以导致治疗中断/延迟，且可能未被眼科专家适当评估。在接受 PD-1/PD-L1 抑制剂治疗的患者研究中，需要制定标准化的眼科评估和眼部毒性管理计划。
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