Serial changes in liquid biopsy-derived variant allele frequency predict immune checkpoint inhibitor responsiveness in the pan-cancer setting.

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.

• Authors: Shumei Kato, Bing Li, Jacob J Adashek, Seong Won Cha, Daniella Bianchi-Frias, Dajun Qian, Lisa Kim, Tiffany W So, Marcus Mitchell, Naoki Kamei, Robert Hoiness, Jayne Hoo, Phillip N Gray, Teruaki Iyama, Masahide Kashiwagi, Hsiao-Mei Lu, Razelle Kurzrock
• Journal: Oncoimmunology (Oncoimmunology) Vol. 11 Issue 1 Pg. 2052410 ( 2022) ISSN: 2162-402X [Electronic] United States
• PMID: 35371621 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.

Chemical References

• Immune Checkpoint Inhibitors

Topics

• Gene Frequency
• Humans
• Immune Checkpoint Inhibitors (pharmacology, therapeutic use)
• Liquid Biopsy
• Mutation
• Neoplasms (drug therapy, genetics, pathology)