A retrospective analysis to evaluate prevalence and correlation between PD-L1 score and tumor mutational burden (TMB) levels in patients with solid tumor malignancies

Abstract

Background: Immunotherapy has been a beacon of hope for many cancers. Recent trials have suggested that PD-L1 expression measured by IHC may predict response to anti-PD 1 (PD-1 & PDL-1) therapy. Response to immunotherapy may have other markers such as Tumor Mutation Burden. Understanding the correlation of these biomarkers may have implications for the application of anti-PD-1 therapies.This study sought to determine TMB and its relation with PD-L1 expression, or lack thereof, in metastatic solid tumors to better define therapeutically relevant patient subgroups. Methods: We evaluated the relationship between PD-L1 expression and TMB levels among patients with metastatic solid tumors being treated at 5 community-based cancer centers. PD-L1 expression was measured by Neogenomics using their immunohistochemistry assay with anti-PD-L1 22C3 antibody. Tumor Mutational Burden (measuring the number of non-synonymous DNA coding sequence changes per megabase of sequenced DNA) was calculated through Foundation One genomic reports. Both tests had low, intermediate & high values assessed. A retrospective chart review was performed of patients with solid tumor malignancies who had both of these tests performed. Results: A Spearman's correlation test was used to assess the relationship between TMB and PD-L1 using a sample of 93 patients. There was no strong correlation between TMB and PD-L1, rz=0.186, p=0.08 which was not statistically significant. Conclusions: There is no correlation between PD-L1 expression level and TMB load. These appear to be independent predictors of possible benefit from checkpoint inhibitors. Studies have also shown Mismatch repair deficiency or Microsatellite instability (MSI-high) to be another independent predictor of benefit from these agents. More studies to evaluate the correlation of these with response from immunotherapy agents are warranted. Immunotherapy specific response data, survival, and predictive biomarkers of response will be reported in a future analysis. This study highlighted the importance to test for both of these markers in order to identify a patient subset that may benefit from immunotherapy.