Predictive value of mRNA expression and dynamic changes from immune related biomarkers in liquid biopsies before and after start of pembrolizumab in stage IV non-small cell lung cancer (NSCLC).

Abstract

BackgroundThe aim of this study was to determine whether mRNA expressions and dynamic changes of immune-related genes before and after starting first-line treatment with the PD-1 inhibitor pembrolizumab in patients with NSCLC were of predictive value.MethodsCD3, CD8, PD-1, PD-L1 and CTLA-4 mRNA expression levels were measured from peripheral blood before and after three weeks of treatment with the PD-1 inhibitor. Univariate and multivariate analyses were performed retrospectively. Response, progression-free survival (PFS) and overall survival (OS) were determined.ResultsIn univariate analysis an increase of CD3 and CD8 mRNA expression after the first cycle of pembrolizumab were each associated with improved PFS and OS. In contrast, patients with no change or with a decrease in CD3 and CD8 mRNA expression showed significantly worse outcome. CD8 mRNA increase remained an independent predictive factor for PFS and OS in the multivariate analysis with p values of 0.011 and 0.006, respectively.ConclusionsAn increase of CD8 mRNA expression predicts favorable outcome after first line monotherapy with pembrolizumab, while no change or decrease might serve as an indicator of poor outcome and might give cause for early treatment escalation for instance by addition of chemotherapy or additional ICI treatment, e.g., against CTLA-4.