Prospective multi-cohort study of predictive value of a 5-gene peripheral blood signature for ICI-response in non-small cell lung cancer

The variability in NSCLC patients responses to immune checkpoint inhibitors (ICIs) necessitates biomarkers to predict the response. Researchers in the USA and China performed transcriptomic profiling of peripheral blood mononuclear cell (PBMC) and buffy coat (BC) samples of NSCLC patients receiving pembrolizumab (plus carboplatin and pemetrexed) in three independent cohorts: a retrospective cohort (PMBCR; n=59), a retrospective validation cohort (BC; n=44), and a prospective validation cohort (PMBCP; n=42). A 5-gene signature (UQCRB, NDUFA3, CDKN2D, FMNL1-DT, and APOL3) was identified that was predictive of response. In the prospective PBMCP cohort, the 5-gene signature demonstrated high accuracy in stratifying patients into responders and non-responders (AUC 0.89; 95% CI 0.80-0.99). Predicted responders exhibited significantly longer progression-free survival and overall survival compared to predicted non-responders. The authors conclude that the 5-gene signature is a biomarker for ICI response in NSCLC.