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

和久井, 大 東京慈恵会医科大学 DOI:info:doi/10.1016/j.cllc.2018.04.014

2021.08.11

概要

Biomarkers for predicting the effect of antieprogrammed cell death 1 monoclonal antibody therapy against nonesmall-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.

Background: Biomarkers for predicting the effect of antieprogrammed cell death 1 (PD-1) monoclonal antibody against nonesmall-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 antiePD-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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