Correlation between tissue PD-L1, TMB, and blood PD-L1, MSI biomarkers in patients with advanced-stage non-small cell lung cancer (NSCLC).

Abstract

e21564 Background: Tissue biomarkers like programmed cell death ligand-1 (PD-L1), microsatellite instability (MSI) and high tumor mutational burden (TMB) are surrogates in identifying patients with non-small cell lung cancer (NSCLC) for treatment with immune checkpoint blockade (ICB) therapy. Although tissue biopsy is widely used for identifying the tumor biology, the invasive nature as well as insufficiency of tissue biopsy specimens limits its application. Liquid biopsy is a minimally invasive procedure and has gained interest in recent times for profiling cancer. We sought to study the correlation in the molecular tumor profile specifically PD-L1, MSI and TMB markers between the tissue and liquid biopsies. Methods: We conducted a retrospective review of patients with Stage 3, 4 and recurrent NSCLC that underwent tissue next generation sequencing (NGS) using Caris life sciences and liquid biopsy using Circulogene molecular diagnostics from January 2018 to December 2019 at East Carolina University. A total of 524 patients were reviewed out of which 199 patients had both liquid and tissue NGS performed at the time of initial diagnosis. TMB high was defined as greater than 10 mut/Mb whereas TMB low as less than or equal to 10 mut/Mb. PD-L1 was divided into negative (0%), 1-49% and ≥50%. The blood MSI was classified as positive or negative. We used frequency table, logistic regression and Pearson bivariate correlation for statistical analysis using SPSS platform. Results: The study cohort had 60% (n = 119) male and 40% (n = 80) female patients of which 53% (n = 105) were Caucasians and 45% (n = 89) were African Americans. A total of 87 patients (44%) had negative tissue PD-L1, 59 patients (30%) had tissue PD-L1 ≥ 50%. A linear correlation was seen between negative tissue PD-L1 and negative blood PD-L1 in 92% of patients (n = 80). However, only 15.3% (n = 9) had correlating tissue PD-L1 and blood PD-L1 ≥ 50%, p = 0.024. The negative blood MSI correlated to low tissue TMB in 83% ( n = 60) whereas positive blood MSI correlated to high tissue TMB in 25% (n = 19), p = 0.023. Conclusions: Our results indicate a linear correlation between tissue PD-L1 and blood PD-L1. Similarly, a linear correlation was seen between blood MSI and tissue TMB. Further studies are needed to elucidate the efficacy of ICB therapy using blood MSI and blood PD-L1 as biomarkers for response to therapy.