Circulating tumor DNA‐based molecular residual disease detection for treatment monitoring in advanced melanoma patients

Abstract

AbstractBackgroundImmune checkpoint inhibitors (ICIs) have substantially improved overall survival in patients with advanced melanoma; however, the lack of biomarkers to monitor treatment response and relapse remains an important clinical challenge. Thus, a reliable biomarker is needed that can risk‐stratify patients for disease recurrence and predict response to treatment.MethodsA retrospective analysis using a personalized, tumor‐informed circulating tumor DNA (ctDNA) assay on prospectively collected plasma samples (n = 555) from 69 patients with advanced melanoma was performed. Patients were divided into three cohorts: cohort A (N = 30), stage III patients receiving adjuvant ICI/observation; cohort B (N = 29), unresectable stage III/IV patients receiving ICI therapy; and cohort C (N = 10), stage III/IV patients on surveillance after planned completion of ICI therapy for metastatic disease.ResultsIn cohort A, compared to molecular residual disease (MRD)‐negative patients, MRD‐positivity was associated with significantly shorter distant metastasis‐free survival (DMFS; hazard ratio [HR], 10.77; p = .01). Increasing ctDNA levels from the post‐surgical or pre‐treatment time point to after 6 weeks of ICI were predictive of shorter DMFS in cohort A (HR, 34.54; p < .0001) and shorter progression‐free survival (PFS) in cohort B (HR, 22; p = .006). In cohort C, all ctDNA‐negative patients remained progression‐free for a median follow‐up of 14.67 months, whereas ctDNA‐positive patients experienced disease progression.ConclusionPersonalized and tumor‐informed longitudinal ctDNA monitoring is a valuable prognostic and predictive tool that may be used throughout the clinical course of patients with advanced melanoma.