Early proliferation of PD-1+ CD8 T cells in peripheral blood as predictive of response to PD-1 inhibition for patients with advanced NSCLC.

Abstract

e20648 Background: Anti PD-1 and PDL-1 antibodies are now established immune targeted therapies for a subset of patients with advanced non-small cell lung cancer (NSCLC). There is a need for predictive biomarkers to better guide patient selection. We profiled peripheral blood samples from patients receiving PD-1 pathway targeted antibodies for lymphocyte subsets and correlated temporal changes with clinical response. Methods: NSCLC patients treated at our institution with PD-1 or PDL-1 inhibitors (nivolumab, pembrolizumab, and atezolizumab) consented to an IRB-approved biomarker profiling protocol. We collected baseline peripheral blood samples before first treatment and subsequently prior to each new treatment cycle until progression of disease or for a maximum of six cycles. Peripheral blood mononuclear cells (PBMCs) were isolated and analyzed by flow cytometry for kinetics of proliferation of PD1+CD8+ T cells. Clinical response to anti PD-1 therapy was classified according to Response Evaluation Criteria in Solid Tumors (RECIST1.1) criteria and correlated with T cell proliferation kinetics. Results: We enrolled 27 patients with baseline characteristics: median age 66, male 70%, smokers 85%, adenocarcinoma 70%; 10 (37%) patients achieved partial response (PR), 7 (26%) had stable disease (SD) and 10 (10%) had disease progression (PD) as best response. There was a > 1.5-fold increase in Ki67+CD8+ T cells expressing PD-1 within 4 weeks of treatment initiation in 80% of patients with PR compared with 30% in patients with SD and 30% in those with PD. Conclusions: Early proliferation of PD1+CD8+ T cells in peripheral blood is a potential pharmacodynamic biomarker of anti PD-1 immunotherapy that could serve as a tool to identify the NSCLC patient subset most likely to respond to PD-1 and PDL-1 inhibitors.