Abstract 1027: Assessment of tumor mutation burden (TMB) based on whole exome sequencing using extracellular vesicles-derived DNA obtained from bronchoalveolar lavage fluid (BALF) in advanced NSCLC patients treated with pembrolizumab

Abstract

Abstract Background: Although multiple immune checkpoint inhibitors showed improved outcomes in patients with high tumor mutational burden (TMB) as well as high PD-L1 expression, obtaining adequate tumor tissue for various molecular testing including next-generation sequencing (NGS) is not a simple issue in patients with advanced non-small cell lung cancer (NSCLC). We aimed to assess TMB based on whole exome sequencing (WES) using extracellular vesicles (EV)-derived DNA isolated from bronchoalveolar lavage fluid (BALF) and determine the correlation of TMB between BALF and tissue. Methods: Patients diagnosed with advanced NSCLC and who were treated with pembrolizumab between December 2018 and December 2021 were included in this multicenter translational cohort study. The correlation of TMB between BALF and tissue measured by WES was evaluated by Spearman’s rank correlation coefficient in matched BALF and tissue samples from 62 patients. We analyzed the association of BALF TMB level with progression-free survival (PFS) and response to pembrolizumab. Results: Of 62 patients, 47 (75.8%) had evaluable tissue TMB and 57 (91.9%) had evaluable BALF TMB. There were no significant differences between BALF and tissue with regards to DNA amounts, estimated library size, mean depth, and uniformity. Median tissue TMB and BALF TMB were 6.02 and 2.16 mut/Mb, respectively. There was a weak positive correlation between tissue TMB and BALF TMB (r=0.23, p < 0.001), whereas BALF TMB found higher correlations with tissue TMB in patients with squamous cell carcinoma (r=0.77, p < 0.001). Neither tissue TMB nor BALF TMB showed significant differences PFS or ORR benefit for treatment with pembrolizumab, however the BALF TMB of patients who had been treated with pembrolizumab for more than 6 months was higher than that of those who did not (p=0.039). Conclusions: The findings suggest that NGS using BALF EV DNA is feasible for TMB calculation to overcome the matter of small biopsy issue in advanced NSCLC patients, which may play a supplementary serve as a potential biomarker of clinical benefit in patients with NSCLC treated with pembrolizumab. Citation Format: Heejoung Kim, Jaeyoung Hur, Wan Seop Kim, In Ae Kim, Dong Il Park, In-Jae Oh, Kye Young Lee. Assessment of tumor mutation burden (TMB) based on whole exome sequencing using extracellular vesicles-derived DNA obtained from bronchoalveolar lavage fluid (BALF) in advanced NSCLC patients treated with pembrolizumab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1027.