Abstract B046: Methylation based circulating tumor DNA serial monitoring correlates with immunotherapy response in non-small cell lung cancer

Abstract Purpose: Circulating tumor DNA (ctDNA) can reflect the genetic and epigenetic composition of malignancies and can serve as a non-invasive biomarker for cancer diagnostics and monitoring. This study aimed to evaluate the utility of a methylation based ctDNA assay as a predictive tool in non-small cell lung cancer (NSCLC) anti-PD1 based immunotherapy monitoring. Methods: We evaluated a cohort of patients with NSCLC treated with anti-PD1 based immunotherapy, from which 108 blood specimens were collected at baseline and during treatment follow-up. Tumor Methylation Scores (TMS) were measured with an amplicon-based, multiplexed cfDNA assay that utilizes quantitative counting templates (QCTs) in conjunction with next-generation sequencing to count the number of methylated molecules at more than 500 genomic locations that are hypermethylated in cancer tissue. The association between TMS and real-world progression-free survival (rwPFS) on therapy was conducted using Cox proportional hazards model and plotted using the Kaplan-Meier method. Results: The change in TMS measured 4-10 weeks post-treatment initiation strongly correlated with immunotherapy response, as measured by rwPFS (p<0.0001), compared to a weaker correlation of imaging RECIST v1.1 measurements with rwPFS (p=0.55). Furthermore, TMS tracked with tumor burden on therapy in real-world cases. Conclusions: In this real-world dataset of NSCLC patients treated with anti- PD1 immunotherapy regimens, TMS scores measured within a 4-10 week window after treatment initiation can be predictive of response to therapy. Beyond this window, the TMS score can be associated with rwPFS and tumor dynamics. Early evidence suggests that changes in the methylation profile may be informative for monitoring occurrence of new somatic mutations. The cases presented demonstrate the applicability of using TMS for serial therapeutic response monitoring. Citation Format: Angela Hsiao, Brian Woodward, Patrick Ye, Matthew Varga, Kevin Lu, Ghaith Altaie, Naomi Searle, Robb Veins, Sydne Langpap, Zeqian Li, Gary Palmer, Hatim Husain. Methylation based circulating tumor DNA serial monitoring correlates with immunotherapy response in non-small cell lung cancer [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B046.