246 Clinicopathologic and genomic correlates of tumor mutational burden and its impact on PD-(L)1 inhibition efficacy in non-small cell lung cancer according to different PD-L1 expression subgroups

Background High tumor mutational burden (TMB) and PD-L1 expression are associated with improved clinical outcomes in patients (pts) with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). However, how TMB performs as a predictive biomarker to ICIs in different PD-L1 expression subgroups is not well characterized. Methods We collected clinicopathologic and genomic data from NSCLCs which underwent targeted NGS and TMB assessment at DFCI. An unbiased recursive partitioning (URP) algorithm was used to investigate an optimal TMB cut-off with respect to objective response rate (ORR) in the subset of pts treated with ICIs. This TMB cut-off was then validated in the prospective POPLAR/OAK cohort. Results Among 3560 NSCLCs identified, median TMB was significantly higher among current smokers compared to former (P 25%, suggesting that TMB differentially impacts response to immunotherapy among PD-L1 high versus low NSCLCs (figure 5). Conclusions The impact of TMB may vary across PD-L1 expression subgroups. Rational integration of TMB and PD-L1 expression may identify NSCLCs with the greatest likelihood of response or resistance to ICIs. Ethics Approval Clinicopathologic data were collected from patients with advanced NSCLC who had consented to a correlative research study (DF/HCC protocol #02-180).