Serial changes in liquid biopsy-derived variant allele frequency predict immune checkpoint inhibitor responsiveness in the pan-cancer setting. (31st December 2022)

• Record Type: Journal Article
• Authors: Kato, Shumei; Li, Bing; Adashek, Jacob J.; Cha, Seong Won; Bianchi-Frias, Daniella; Qian, Dajun; Kim, Lisa; so, Tiffany W; Mitchell, Marcus; Kamei, Naoki; Hoiness, Robert; Hoo, Jayne; Gray, Phillip N.; Iyama, Teruaki; Kashiwagi, Masahide; Lu, Hsiao-Mei; Kurzrock, Razelle
• Is Part Of: Oncoimmunology. Volume 11:Number 1(2022)
• Publication Date: 2022-12-31
• Subjects: Immune checkpoint inhibitor -- liquid biopsy -- response -- cancer; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2022.2052410
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: Major immunotherapy challenges include a limited number of predictive biomarkers and the unusual imaging features post-therapy, such as pseudo-progression, which denote immune infiltrate-mediated tumor enlargement. Such phenomena confound clinical decision-making, since the cancer may eventually regress, and the patient should stay on treatment. We prospectively evaluated serial, blood-derived cell-free DNA (cfDNA) (baseline and 2–3 weeks post-immune checkpoint inhibitors [ICIs]) for variant allele frequency (VAF) and blood tumor mutation burden (bTMB) changes (next-generation sequencing) (N = 84 evaluable patients, diverse cancers). Low vs. high cfDNA-derived average adjusted ΔVAF (calculated by a machine-learning model) was an independent predictor of higher clinical benefit rate (stable disease ≥6 months/complete/partial response) (69.2% vs. 22.5%), and longer median progression-free (10.1 vs. 2.25 months) and overall survival (not reached vs. 6.1 months) (all P < .001, multivariate). bTMB changes did not correlate with outcomes. Therefore, early dynamic changes in cfDNA-derived VAF were a powerful predictor of pan-cancer immunotherapy outcomes. Brief summary: Liquid biopsy to predict immunotherapy response.