使用抗PD-1/PD-L1或CTLA-4免疫检查点抑制（ICI）的不同联合疗法广泛用于转移性肾细胞癌（mRCC）患者。在缺乏既定生物标志物的情况下，免疫相关不良事件 (irAE) 已被讨论为潜在的缓解预测因素。在这项回顾性队列研究中，134 名 mRCC 患者接受 ICI 治疗（纳武单抗、伊匹单抗和纳武单抗、帕博利珠单抗和阿西替尼或对 2015 年至 2021 年期间的 Avelumab 和 Axitinib）进行了分析。为了检验 irAE 作为总生存期 (OS) 和无进展生存期 (PFS) 预测因子的效用，应用了单独的 Kaplan-Meier 分析和 Cox 比例回归分析。 12周后进行标志性分析，以减少永生时间偏差。在85名患者（63.4%）中观察到irAE。最常见的是皮肤（n = 52，38.8%）、内分泌（n = 33，24.6%）和肝脏（n = 19，14.2%）irAE。在 Kaplan-Meier 分析中，与非 irAE 组（5 个月，95% CI，3.56-6.44，P < 0.001）相比，经历 irAE 的患者表现出良好的中位 PFS（15 个月，95% CI，9.91-20.09）。非 irAE 组的中位 OS 为 25 个月（95% CI，16.79-33.21），而 irAE 组未达到该值 (P = .002)。在多变量分析中，任何 irAE 的存在均与良好的 PFS（HR 0.46 [95% CI，0.26-0.82] P = .008）和 OS（HR：0.28 [95% CI，0.12-0.63] P = .002）相关）， 分别。 12 周后的标志性分析显示出不同的结果，具体取决于标志性时间 irAE 组的分类。mRCC 患者接受 ICI 治疗时出现 irAE 与更好的 PFS 和 OS 相关。因此，可控的 irAE 不应成为提前停止 ICI 治疗的原因，因为它们似乎表明了良好的结果。考虑到 irAE 的时间依赖性对于估计其作为预测标记的价值至关重要。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

Different combination therapies using anti - PD-1 / PD-L1 or CTLA-4 immune checkpoint inhibition (ICI) are widely used in patients with metastatic renal cell carcinoma (mRCC). In the absents of established biomarkers, immune-related adverse events (irAEs) have been discussed as potential predictors of response.In this retrospective cohort study, data of 134 patients with mRCC undergoing ICI treatment (Nivolumab, Ipilimumab and Nivolumab, Pembrolizumab and Axitinib or Avelumab and Axitinib) between 2015 and 2021 were analyzed. To examine the utility of irAEs as predictors of overall survival (OS) and progression-free survival (PFS), separate Kaplan-Meier analyses and Cox proportional regression analyses were applied. Landmark analysis was conducted after 12 weeks to reduce immortal time bias.irAEs were observed in 85 patients (63.4%). Cutaneous (n = 52, 38.8%), endocrine (n = 33, 24.6%) and hepatic (n = 19, 14.2%) irAEs were most commonly observed. In Kaplan-Meier analysis, patients experiencing irAEs showed favorable median PFS (15 months, 95% CI, 9.91-20.09) compared to the non-irAE group (5 months, 95% CI, 3.56-6.44, P < .001). The median OS was 25 months (95% CI, 16.79-33.21) in the non-irAE group, while it was not reached in the irAE group (P = .002). In multivariable analysis, the presence of any irAE was associated with favorable PFS (HR 0.46 [95% CI, 0.26-0.82] P = .008) and OS (HR: 0.28 [95% CI, 0.12-0.63] P = .002), respectively. Landmark analysis after 12 weeks showed mixed results depending on the classification of the irAE group at the landmark time.The presence of irAEs under ICI therapy in patients with mRCC is associated with better PFS and OS. Thus, manageable irAEs should not be cause for premature discontinuation of ICI therapy, as they seem to indicate favorable outcomes. Considering the time-dependent nature of irAEs is crucial estimating their value as predictive markers.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.