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

• Published in: Clinical lung cancer Vol. 19; no. 5; pp. 410 - 417.e1
• Main Authors: Okuma, Yusuke, Wakui, Hiroshi, Utsumi, Hirofumi, Sagawa, Yukiko, Hosomi, Yukio, Kuwano, Kazuyoshi, Homma, Sadamu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2018
• Subjects: Adenocarcinoma - blood; Adenocarcinoma - drug therapy; Adenocarcinoma - secondary; Aged; Aged, 80 and over; Anti-programmed cell death 1 monoclonal antibody therapy; Antineoplastic Agents, Immunological - therapeutic use; B7-H1 Antigen - blood; Biomarker; Biomarkers, Tumor - blood; Carcinoma, Large Cell - blood; Carcinoma, Large Cell - drug therapy; Carcinoma, Large Cell - secondary; Carcinoma, Non-Small-Cell Lung - blood; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - secondary; Carcinoma, Squamous Cell - blood; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - secondary; Female; Follow-Up Studies; Humans; Lung Neoplasms - blood; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local - blood; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - pathology; Nivolumab; Nivolumab - therapeutic use; NSCLC; Prognosis; Prospective Studies; sPD-L1; Survival Rate; Anti-programmed cell death 1 monoclonal antibody therapy; Biomarker; NSCLC; Nivolumab; sPD-L1
• ISSN: 1525-7304; 1938-0690; 1938-0690
• DOI: 10.1016/j.cllc.2018.04.014

Biomarkers for predicting the effect of anti–programmed cell death 1 monoclonal antibody therapy against non–small-cell lung cancer (NSCLC) are urgently required. We prospectively studied the baseline plasma soluble programmed cell death ligand 1 (sPD-L1) levels from 39 NSCLC patients as a predictive marker of nivolumab therapy. The clinical benefit from nivolumab therapy was significantly associated with the baseline plasma sPD-L1 levels. Plasma sPD-L1 levels could represent a novel predictive marker for nivolumab therapy against NSCLC. 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. 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. 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. 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.