Association of circulating tumor DNA kinetics with disease recurrence in patients with stage IIIB/C/IV melanoma treated with adjuvant immunotherapy in Checkmate 238.

作者：Mahrukh M. Syeda, Jennifer Wiggins, Josephine Alegun, Saim Ali, Hao Tang, Sheen Wang, Kao-Tai Tsai, Keyur Desai, Sonia Dolfi, Daniel J. Tenney, Paolo A. Ascierto, James Larkin, Michele Del Vecchio, Jeffrey S. Weber, David Polsky · 发表于：Journal of Clinical Oncology · 年份：2023 · DOI：10.1200/jco.2023.41.16_suppl.9577 · 被引用次数：6 · 研究领域：Cancer Genomics and Diagnostics、Cancer Immunotherapy and Biomarkers、Immunotherapy and Immune Responses

9577 Background: In patients (pts) with resected, stage III/IV melanoma receiving adjuvant immunotherapy, pre-treatment (pre-Tx) and on-treatment (on-Tx) circulating tumor DNA (ctDNA) combined with tumor features were evaluated to predict recurrence risk. Methods: We used analytically validated, mutation-specific droplet digital PCR (ddPCR) assays to measure ctDNA in pre- and on-Tx plasma samples from pts with resected stage IIIB/C/IV melanoma enrolled in CheckMate 238 (NCT02388906) receiving either adjuvant Nivolumab (NIVO) or Ipilimumab (IPI). Assay choice was based on detection of one of the 7 melanoma hot-spot mutations in pt tumors: BRAF V600E/K, NRAS Q61R/L/K, or TERT C228T/C250T. We evaluated associations between ctDNA detection, recurrence free survival (RFS), distant metastasis free survival (DMFS), and known immunotherapy tumor biomarkers including PD-L1, IFNg gene signature, CD8, and tumor mutational burden. Associations between ctDNA kinetics and RFS/DMFS were analyzed using Kaplan-Meier and Cox regression models. Results: Mutations were identified in 87% of tumors. ctDNA was detected in pre-Tx samples from 94/753 (12.5%) pts. Pre-Tx ctDNA was significantly associated with higher stage of disease, LDH ≥ ULN, PD-L1 < 5%, and tumor IFNg-RNA signature expression below the median. Detection of pre-Tx ctDNA was associated with shorter RFS and DMFS in both NIVO and IPI arms compared to undetectable ctDNA (Table). ctDNA detection on-Tx (week (w) 3, 7, 13, 25, 37, 49) ...