Serial changes in liquid biopsy-derived variant allele frequency predict immune checkpoint inhibitor responsiveness in the pan-cancer setting. Oncoimmunology 2022;11(1):2052410
Date
04/05/2022Pubmed ID
35371621Pubmed Central ID
PMC8966985DOI
10.1080/2162402X.2022.2052410Scopus ID
2-s2.0-85127471090 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
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.
Author List
Kato S, Li B, Adashek JJ, Cha SW, Bianchi-Frias D, Qian D, Kim L, So TW, Mitchell M, Kamei N, Hoiness R, Hoo J, Gray PN, Iyama T, Kashiwagi M, Lu HM, Kurzrock RAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Gene FrequencyHumans
Liquid Biopsy
Mutation
Neoplasms