外周血标志物可识别免疫检查点抑制剂治疗晚期非小细胞肺癌相关免疫毒性的风险。
Peripheral Blood Markers Identify Risk of Immune-Related Toxicity in Advanced Non-Small Cell Lung Cancer Treated with Immune-Checkpoint Inhibitors.
机构信息
Medical Oncology 2, Veneto Institute of Oncology IOV, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua, Italy.
Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
出版信息
Oncologist. 2019 Aug;24(8):1128-1136. doi: 10.1634/theoncologist.2018-0563. Epub 2019 Apr 23.
BACKGROUND
Immune-checkpoint inhibitors (ICIs) are now standard of care for advanced non-small cell lung cancer (NSCLC). Unfortunately, many patients experience immune-related adverse events (irAEs), which are usually mild and reversible, but they require timely management and may be life threatening. No predictive markers of irAEs are available.
MATERIALS AND METHODS
The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were evaluated in patients with NSCLC consecutively treated with ICIs. Prespecified cutoff values of NLR and PLR were used and related to outcome and onset of irAEs. A control group of patients with advanced NSCLC not receiving ICIs was included.
RESULTS
The study included 184 patients: 26 (14.1%) received pembrolizumab upfront, and 142 (77%) received ICIs (pembrolizumab, nivolumab or atezolizumab) after one or more lines of chemotherapy. The median number of ICIs cycles was six (range, 1-61). The median progression-free survival and overall survival were 4.8 (95% CI, 3.4-6.3) and 20.6 (95% CI, 14.7-26.5) months, respectively. Sixty patients (32.6%) developed irAEs, mainly grade 1-2 (65.0%), causing ICI interruption in 46 cases (25.0%). Low NLR and low PLR at baseline were significantly associated with the development of irAEs (odds ratio [OR], 2.2; = .018 and OR, 2.8; = .003, respectively). Multivariate analyses confirmed PLR as independent predictive marker of irAEs (OR, 2.3; = .020).
CONCLUSION
NLR and PLR may predict the appearance of irAEs in non-oncogene-addicted aNSCLC, although this conclusion warrants prospective validation.
IMPLICATIONS FOR PRACTICE
This study was designed to investigate the role of blood biomarkers in predicting the occurrence of immune-related adverse events (irAEs) in patients with advanced non-small cell lung cancer receiving immunotherapy. The results of the study suggest a potential predictive role of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as markers for irAE development in this category of patients. These data provide rationale for an easy and feasible application to be validated in clinical practice.
背景
免疫检查点抑制剂（ICI）现已成为晚期非小细胞肺癌（NSCLC）的标准治疗方法。不幸的是，许多患者会出现免疫相关不良反应（irAEs），这些不良反应通常是轻微且可逆的，但需要及时管理，并且可能危及生命。目前尚无 irAEs 的预测标志物。
材料和方法
连续接受 ICI 治疗的 NSCLC 患者的中性粒细胞与淋巴细胞比值（NLR）和血小板与淋巴细胞比值（PLR）进行了评估。使用 NLR 和 PLR 的预设临界值，并将其与结局和 irAEs 的发生相关联。还纳入了一组未接受 ICI 治疗的晚期 NSCLC 患者作为对照组。
结果
该研究纳入了 184 例患者：26 例（14.1%）患者接受了帕博利珠单抗一线治疗，142 例（77%）患者在一线或多线化疗后接受了 ICI（帕博利珠单抗、纳武利尤单抗或阿替利珠单抗）治疗。ICI 治疗的中位周期数为 6 个（范围 1-61）。中位无进展生存期和总生存期分别为 4.8（95%CI，3.4-6.3）和 20.6（95%CI，14.7-26.5）个月。60 例（32.6%）患者发生了 irAEs，主要为 1-2 级（65.0%），导致 46 例（25.0%）患者中断 ICI 治疗。基线时 NLR 和 PLR 较低与 irAEs 的发生显著相关（比值比 [OR]，2.2；P=.018 和 OR，2.8；P=.003）。多变量分析证实 PLR 是 irAEs 的独立预测标志物（OR，2.3；P=.020）。
结论
NLR 和 PLR 可能预测非驱动基因 NSCLC 患者对免疫治疗出现 irAEs，尽管这一结论需要前瞻性验证。
意义
本研究旨在探讨血液生物标志物在预测接受免疫治疗的晚期非小细胞肺癌患者发生免疫相关不良事件（irAEs）中的作用。研究结果表明，中性粒细胞与淋巴细胞比值和血小板与淋巴细胞比值作为这一类患者 irAE 发生的标志物具有潜在的预测作用。这些数据为在临床实践中进行验证提供了一个简单可行的应用依据。
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