618 Circulating tumor DNA as a predictive biomarker of recurrence for resected high-risk melanoma

<h3>Background</h3> Despite improved outcomes for resectable advanced melanoma with effective systemic therapy, there are no good biomarkers currently to predict response to adjuvant therapy. Circulating tumor DNA (ctDNA) is an emerging biomarker in melanoma. At Cleveland Clinic, we developed a ctDNA next generation sequencing panel specific for melanoma genes and prospectively quantified minimal residual disease by identifying somatic mutations in ctDNA collected from patients as they underwent treatment and follow-up. <h3>Methods</h3> Patients with stage 3 melanoma were prospectively enrolled on our IRB approved protocol from 2019 to 2021 after surgery and had blood samples collected, at baseline, 3 months, 6 months, 18 months after surgery, and an additional sample was collected if clinical recurrence was detected. Fluxion Biosciences, Inc. conducted ctDNA analysis by identifying melanoma-specific somatic mutations in blood samples by a customized ERASE-Seq method. Variables underwent analysis employing frequencies, percentages, and measures of central tendency. Clinical patient outcomes were collected prospectively and confirmed through chart review. <h3>Results</h3> Forty-three patients had blood samples collected. Median age was 58. 69.7% were male. Mean tumor Breslow depth was 2.4 mm. Median follow-up was 38 months. Our cohort included patients with stage 3A (9.3%), s 3B (46.5%), 3C (41.8%), and 3D (2.3%). 72% underwent wide excision with sentinel lymph node biopsy, 11.6% had lymph node dissection and 16.2% underwent lymph node dissection alone. 36 patients received active adjuvant therapy. Adjuvant therapy included, anti-PD-1 immune checkpoint inhibitors (82.9%) and combined targeted therapy (17%). Thirteen (30.2%) patients experienced recurrence confirmed by biopsy. The median time to recurrence was 14.5 months. ctDNA was positive in 39 patients (90.6%) at baseline, 12 (30.7%) patients developed recurrence. ctDNA screening was negative in 4 (8.3%) patients at baseline, subsequently, one of these patients experienced recurrence. Interestingly, the number of somatic mutations progressively increased in absolute quantity in all 12 patients who developed recurrence over their time on in follow-up. <h3>Conclusions</h3> Our ctDNA gene panel quantified circulating melanoma genes in patients following surgery for high-risk stage 3 disease. Additional study is needed to develop algorithms to help predict recurrence or help early ascertainment of relapse to guide treatment and follow-up for patients. Further studies are needed to determine specificity and sensitivity of this diagnostic to guide use in the treatment of melanoma <h3>Ethics Approval</h3> This study was approved by Cleveland Clinic institution’s Ethics Board; approval number IRB 3164. <h3>Consent</h3> Written informed consent was obtained from patients for publication of this abstract and any accompanying images.