Department of Health Statistics, Second Military Medical University, Shanghai, China.
Department of Medical Service, Naval Hospital of Eastern theater, Zhoushan, China.
Cancer Med. 2021 Dec;10(24):8754-8762. doi: 10.1002/cam4.4343. Epub 2021 Nov 29.
Immune checkpoint inhibitors (ICIs) have elicited durable antitumor responses in multiple types of cancers. However, ICIs could also induce potential toxicities that involve all organs, including renal system. In this study, we aimed to conduct a comprehensive description of the ICIs-induced renal toxicities and the potential effects of chemotherapy.
We conducted a pharmacovigilance study based on US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database between 01 January 2014 and 30 June 2019. Disproportionality analysis was used to assess the association between ICIs and renal adverse events (AEs), including reporting odds ratio (ROR) and information component (IC). ROR and IC are, respectively, 95% confidence interval lower end of ROR and IC. If the value of ROR exceeding one or IC higher than zero, then a signal was considered statistically significant.
A total of 30,602,758 reports were extracted from the database, with 4578 reports for ICIs-associated renal AEs. Renal AEs were more frequently reported in anti-PD-1/PD-L1 versus anti-CTLA-4 monotherapy group (ROR: 1.75, 95% CI: 1.52-2.01). Similarly, renal AEs were more commonly reported in ICIs polytherapy other than monotherapy group (ROR: 1.18, 95% CI: 1.10-1.27). Notably, ICIs plus chemotherapy strategies reported more renal toxicities compared to sole ICIs regimens (ROR: 1.30, 95% CI: 1.17-1.45), whereas exhibited lower fatality outcome rates. Importantly, acute kidney injury (1139, 24.88%) and renal failure (464, 10.14%) were the top two most commonly reported ICIs-associated renal AEs, and also observed with the top two highest level of fatality outcome rates.
A spectrum of renal AEs was detected in ICIs regimens and could be reinforced by ICIs combination. Compared to sole ICIs regimens, ICIs plus chemotherapy strategy reported more renal toxicities but lower fatality outcome rates. With the increasing popularity of ICIs especially combination strategies, it is vital important for clinicians to guarantee balance between durable clinical effects and potential renal toxicities in latest immunotherapy strategies.
免疫检查点抑制剂（ICIs）在多种癌症中引发了持久的抗肿瘤反应。然而，ICI 也可能引起涉及所有器官的潜在毒性，包括肾脏系统。在这项研究中，我们旨在全面描述 ICI 诱导的肾毒性和化疗的潜在影响。
我们基于美国食品和药物管理局（FDA）不良事件报告系统（FAERS）数据库进行了一项药物警戒研究，时间范围为 2014 年 1 月 1 日至 2019 年 6 月 30 日。比例失衡分析用于评估 ICI 与肾脏不良事件（AE）之间的关联，包括报告比值比（ROR）和信息分量（IC）。ROR 和 IC 分别是 ROR 的 95%置信区间下限和 IC。如果 ROR 值超过 1 或 IC 值高于 0，则认为存在统计学意义的信号。
从数据库中提取了 30602758 份报告，其中有 4578 份报告与 ICI 相关的肾脏 AE。与抗 PD-1/PD-L1 单药治疗组相比，肾 AE 更常发生在抗 PD-1/PD-L1 联合治疗组（ROR：1.75，95%CI：1.52-2.01）。同样，ICI 联合治疗组比单药治疗组更常见肾 AE（ROR：1.18，95%CI：1.10-1.27）。值得注意的是，与单独使用 ICI 方案相比，ICI 联合化疗方案报告的肾毒性更多（ROR：1.30，95%CI：1.17-1.45），但死亡率较低。重要的是，急性肾损伤（1139 例，24.88%）和肾衰竭（464 例，10.14%）是报告最多的两种 ICI 相关肾 AE，也是死亡率最高的两种 AE。
在 ICI 方案中检测到一系列肾 AE，并且可以通过 ICI 联合治疗来加强。与单独使用 ICI 方案相比，ICI 联合化疗方案报告的肾毒性更多，但死亡率较低。随着 ICI 的广泛应用，特别是联合治疗策略的应用，临床医生在最新的免疫治疗策略中平衡持久的临床效果和潜在的肾毒性至关重要。
