Neutrophil-lymphocyte ratio kinetics in patients with advanced solid tumours on phase I trials of PD-1/PD-L1 inhibitors
Neutrophil-lymphocyte ratio kinetics in patients with advanced solid tumours on phase I trials of PD-1/PD-L1 inhibitors
复制标题
DOI：
10.1016/j.ejca.2017.11.012
复制
发表时间：
2018-01-01
影响因子：
8.4
通讯作者：
Lopez, Juanita
中科院分区：
文献类型：
--
作者：
Ameratunga, Malaka;Chenard-Poirier, Maxime;Lopez, Juanita
背景资料：虽然嗜中性粒细胞-淋巴细胞比率（NLR）在许多肿瘤学环境中具有预后意义，但其在免疫治疗时代的意义尚不清楚。从机制上讲，PD-1/PD-L1抑制剂可能会改变NLR。我们试图研究PD-1/PD-L1抑制剂治疗晚期实体瘤患者的NLR动力学。方法：回顾了三个研究中心I期试验中PD-1/PD-L1抑制剂治疗患者的电子记录。高NLR（hNLR）预定义为>5。单变量logistic回归模型用于毒性、缓解分析，考克斯模型用于总生存期（OS）和无进展生存期分析。进行了标志性分析（第2、3周期）。结果：hNLR患者的中位OS为8.5个月，低NLR患者的中位OS为19.4个月（风险比[HR] Z 1.85，95%置信区间[CI] 1.15-2.96，p = 0.01）。在界标分析中，hNLR在所有时间点与较差OS显著相关，随时间推移的影响程度相似（p < 0.05）。在多变量分析中，NLR与OS相关（HR 1.06，95% CI 1.01-1.11，p = 0.01）。NLR与免疫毒性增加无关。纵向上，NLR与反应相关：与非反应者相比，反应者的NLR每月下降0.09（95%CI：-0.15至-0.02; p = 0.01）。结论：在接受PD-1/PD-L1阻断的晚期恶性肿瘤患者中，基线和治疗期间的hNLR具有不良预后。重要的是，NLR在免疫治疗应答者中随时间推移而降低。综上所述，这些数据表明，基线和纵向NLR可能作为一种独特的生物标志物，有助于接受免疫治疗的患者做出临床决策。(C)2017爱思唯尔有限公司版权所有
Background: Although the neutrophil-lymphocyte ratio (NLR) is prognostic in many oncological settings, its significance in the immunotherapy era is unknown. Mechanistically, PD-1/PD-L1 inhibitors may alter NLR. We sought to characterise NLR kinetics in patients with advanced solid tumours treated with PD-1/PD-L1 inhibitors.Methods: Electronic records of patients treated with PD-1/PD-L1 inhibitors on phase I trials across three sites were reviewed. A high NLR (hNLR) was predefined as >5. Univariate logistic regression models were used for toxicity, response analyses and Cox models for overall survival (OS) and progression-free survival analyses. Landmark analyses were performed (cycle two, three). Longitudinal analysis of NLR was performed utilising a mixed effect regression model.Results: The median OS for patients with hNLR was 8.5 months and 19.4 for patients with low NLR, (hazard ratio [HR] Z 1.85, 95% confidence interval [CI] 1.15-2.96, p = 0.01). On landmark analysis, hNLR was significantly associated with inferior OS at all time points with a similar magnitude of effect over time (p < 0.05). On multivariate analysis, NLR was associated with OS (HR 1.06, 95% CI 1.01-1.11, p = 0.01). NLR did not correlate with increased immune toxicity. Longitudinally, NLR correlated with response: NLR decreased by 0.09 (95% CI: -0.15 to -0.02; p = 0.01) per month in responders compared with non-responders.Conclusions: hNLR at baseline and during treatment is adversely prognostic in patients with advanced malignancies receiving PD-1/PD-L1 blockade. Importantly, NLR reduced over time in responders to immunotherapy. Taken together, these data suggest that baseline and longitudinal NLR may have utility as a unique biomarker to aid clinical decision-making in patients receiving immunotherapy. (C) 2017 Elsevier Ltd. All rights reserved.