Soluble immune biomarkers to anti-PD1 treatment in non-small cell lung cancer (NSCLC)

Background: Anti-PD1 antibodies has become the standard second line treatment for advanced Non-Small-Cell Lung Cancer (NSCLC). The efficacy of these treatments seems to be higher in tumors expressing PDL1. However, the difficulty to achieve tumour samples for the analysis of PDL1 is a barrier for precise oncology. The aim of this study was to evaluate the utility of circulating biomarkers such as sPDL1, sPDL2, sCD80 and sHVEM as predictors of response to PD1 blockers in NSCLC. Methods: Blood samples were collected before treatment from 34 NSCLC pts who received anti-PD1 therapy (second line). Plasma levels of four immune-markers were measured through ELISA and Multiplex bead-based assays. When needed, continuous variables were categorized using the median or quartiles as a cut-off. Non parametric test were used for correlations between analytical variables and clinical-pathological parameters, response rate. For survival analysis (progression free- PFS or overall survival - OS) Kaplan Meier curves and long-rank test were performed. Results: Median age of the pts included in the study was 64y, 73% were males and 67% adenocarcinomas. Median plasma levels of PDL1, PDL2, CD80 and HVEM were 1.31, 1.12, 0.197 and 0.451 ng/ml, respectively. No relevant association between clinic-pathological parameters and the plasma markers analyzed were found. Interestingly, response rate in patients with sPDL1 in the first quartile (Q1) was 11%, whereas for those in the Q2 and Q3 were 44% and 40%, respectively and the percentage raises to 50% in the Q4. Patients with higher plasma levels of CD80 had a significant increase in PFS compared to those with sCD80 below the median (14.50 vs 1.70 months, p = 0.026, respectively). Conclusions: In conclusion, circulating immune markers can be reliable detected in plasma of advanced NSCLC pts. In pts treated with anti-PD1 antibodies, sPDL1 and sCD80 seem to be related to the degree of response or PFS. Further investigations to assess the role of these biomarkers in the context of immunotherapy are needed. Legal entity responsible for the study: Comité Etico de Investigacion de Hospital Arnau de Vilanova de Valencia, Spain. Funding: grant PI15-00753 from Instituto de Salud Carlos III and Arnal Planelles Foundation. Disclosure: All authors have declared no conflicts of interest.