Division of Respiratory Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
Division of Respiratory Medicine, Mito Medical Center, University of Tsukuba–Mito Kyodo General Hospital, Mito, Japan
Pol Arch Intern Med. 2021 Oct 27;131(10). doi: 10.20452/pamw.16049. Epub 2021 Jun 28.
Introduction: There is an unmet clinical need to identify biomarkers predicting which patients with non–small cell lung cancer (NSCLC) would benefit from treatment with immune checkpoint inhibitors (ICPIs). Objectives: The purpose of this study was to draw a detailed time to treatment failure (TTF) curve with information on the changes in peripheral eosinophil expression during ICPI treatment for NSCLC, and to clarify whether eosinophil expression can predict prolonged TTF. Patients and methods: In 259 patients with NSCLC treated with ICPI therapy, peripheral eosinophil counts and percentages at the time of each ICPI administration were evaluated from the beginning of ICPI treatment up to TTF. Univariable and multivariable analyses were performed to identify clinical factors associated with TTF. Results: Patients receiving ICPI monotherapy (n = 180) were divided into 3 groups (TTF ≤6 weeks, TTF >6 weeks and ≤24 weeks, and TTF >24 weeks) and the number of patients with an eosinophil percentage of 5% or more within 6 weeks of ICPI therapy initiation was significantly different among these groups. In univariable and multivariable analyses, performance status of 0 to 1, immune-related adverse event not requiring ICPI discontinuation as well as an eosinophil percentage of 5% or more and an eosinophil count of 330/μ or more within 6 weeks of ICPI therapy initiation were significant favorable factors for prolonged TTF. In patients treated with combination therapy of ICPI and chemotherapy (n = 79), the number of patients with an eosinophil percentage of 5% or more within 12 weeks of therapy initiation was significantly different between patients with a TTF of up to 12 weeks and those with a more prolonged TTF. However, the only significant favorable factor for TTF was female sex. Conclusions: In NSCLC patients treated with ICPI therapy, particularly ICPI monotherapy, eosinophil measurements during treatment might be useful for predicting prolonged TTF.
临床需要识别生物标志物，以预测哪些非小细胞肺癌（NSCLC）患者将从免疫检查点抑制剂（ICPI）治疗中获益。目的：本研究旨在绘制一幅详细的治疗失败时间（TTF）曲线，该曲线包含了 NSCLC 患者接受 ICPI 治疗期间外周血嗜酸性粒细胞表达变化的信息，并阐明嗜酸性粒细胞表达是否可以预测 TTF 延长。患者和方法：在 259 例接受 ICPI 治疗的 NSCLC 患者中，从 ICPI 治疗开始至 TTF，评估了每次 ICPI 给药时外周血嗜酸性粒细胞计数和百分比。进行单变量和多变量分析，以确定与 TTF 相关的临床因素。结果：接受 ICPI 单药治疗的患者（n=180）分为 3 组（TTF≤6 周、TTF＞6 周且≤24 周和 TTF＞24 周），在 ICPI 治疗开始后 6 周内嗜酸性粒细胞百分比≥5%的患者数量在这 3 组之间存在显著差异。在单变量和多变量分析中，0 至 1 分的表现状态、不需要停止 ICPI 的免疫相关不良事件以及 ICPI 治疗开始后 6 周内嗜酸性粒细胞百分比≥5%和嗜酸性粒细胞计数≥330/μL 是 TTF 延长的显著有利因素。在接受 ICPI 联合化疗治疗的患者（n=79）中，在治疗开始后 12 周内嗜酸性粒细胞百分比≥5%的患者数量在 TTF 为 12 周及以上的患者和 TTF 更长的患者之间存在显著差异。然而，唯一对 TTF 有显著有利影响的因素是女性。结论：在接受 ICPI 治疗的 NSCLC 患者中，特别是接受 ICPI 单药治疗的患者，治疗期间的嗜酸性粒细胞检测可能有助于预测 TTF 延长。
