Soluble Programmed Cell Death Ligand 1 as a Novel Biomarker for Nivolumab Therapy for Non–Small-cell Lung Cancer

无容量 医学 肺癌 单克隆抗体 内科学 癌症研究 肿瘤科 生物标志物 曲线下面积 癌症 抗体 免疫疗法 胃肠病学 免疫学 化学 生物化学
作者
Yusuke Okuma,Hiroshi Wakui,Hirofumi Utsumi,Yukiko Sagawa,Yukio Hosomi,Kazuyoshi Kuwano,Sadamu Homma
出处
期刊:Clinical Lung Cancer [Elsevier]
卷期号:19 (5): 410-417.e1 被引量:121
标识
DOI:10.1016/j.cllc.2018.04.014
摘要

Background Biomarkers for predicting the effect of anti–programmed cell death 1 (PD-1) monoclonal antibody against non–small-cell lung cancer (NSCLC) are urgently required. Although it is known that the blood levels of soluble programmed cell death ligand 1 (sPD-L1) are elevated in various malignancies, the nature of sPD-L1 has not been thoroughly elucidated. We investigated the significance of plasma sPD-L1 levels as a biomarker for anti–PD-1 monoclonal antibody, nivolumab therapy. Patients and Methods The present prospective study included 39 NSCLC patients. The patients were treated with nivolumab at the dose of 3 mg/kg every 2 weeks, and the effects of nivolumab on NSCLC were assessed according to the change in tumor size, time to treatment failure (TTF), and overall survival (OS). The baseline plasma sPD-L1 concentration was determined using an enzyme-linked immunosorbent assay. Results The area under the curve of the receiver operating characteristic curve was 0.761. The calculated optimal cutoff point for sPD-L1 in the plasma samples was 3.357 ng/mL. Of the 39 patients, 59% with low plasma sPD-L1 levels achieved a complete response or partial response and 25% of those with high plasma sPD-L1 levels did so. In addition, 22% of the patients with low plasma sPD-L1 levels developed progressive disease compared with 75% of those with high plasma sPD-L1 levels. The TTF and OS were significantly longer for those patients with low plasma sPD-L1 levels compared with the TTF and OS for those with high plasma sPD-L1 levels. Conclusion The clinical benefit from nivolumab therapy was significantly associated with the baseline plasma sPD-L1 levels. Plasma sPD-L1 levels might represent a novel biomarker for the prediction of the efficacy of nivolumab therapy against NSCLC.
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