Clinical validation of a tissue-agnostic genome-wide methylome enrichment assay to monitor response to pembrolizumab
Year: 2026
Type: article
Abstract: Immunotherapy has significantly improved the treatment of metastatic solid tumors; however, detecting early signs of response to enable timely intervention for resistant tumors remains challenging. A blood-only circulating tumor DNA (ctDNA) test may provide a rapid assessment of tumor response without reliance on matched tumor tissue. We applied a tissue-agnostic, genome-wide methylation enrichment assay, based on cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq), to plasma samples from patients in a phase 2 trial evaluating pembrolizumab across multiple solid tumors (NCT02644369). A decrease in ctDNA from baseline to pre-cycle 3 was significantly associated with higher objective response and clinical benefit rates and longer progression-free and overall survival in univariate analyses, with these associations remaining significant in multivariable models except for overall survival. These results validate a commercial-grade, tissue-agnostic plasma cfDNA methylation platform for immunotherapy response monitoring, which may facilitate earlier, more informed treatment decisions and improve patient outcomes.
Source: npj Precision Oncology
Authors: Eric Y. Stutheit-Zhao, Yongqi Zhong, Collin A. Melton, Elizabeth D. Lightbody, Michael A. Hinterberg, Yarong Wang, Owen Hall, Eduardo V. Sosa, Jeremy B. Provance, Junjun Zhang, Abel Licon, Zhihui Amy Liu, Albiruni R. Abdul Razak, Anna Spreafico, Philippe L. Bedard, Aaron R. Hansen, Stephanie Lheureux, Pamela S. Ohashi, Alan Williams, Scott V. Bratman, Brian A. Allen, Jing Zhang, Daniel D. De Carvalho, Anne-Renee Hartman, Lillian L. Siu, Enrique Sanz-Garcia
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,090
OpenAlex ID: W7128812971