Abstract 1984: Correlating circulating tumor cell dynamics with clinical outcomes in patients with advanced stage melanoma

Abstract Background: Liquid biopsies in advanced solid tumors can provide a unique noninvasive approach to monitor disease burden over time. Detection and capturing circulating tumor cells (CTCs) in melanoma patients have faced many challenges and limitations. In our study, we use our novel, high-sensitivity, CTC capturing technology to assess numerical heterogeneity of serially collected CTCs in advanced stage melanoma patients undergoing systemic treatment and correlate CTC dynamics with tumor response and risk of disease progression. Methods: We utilize a unique microfluidic exclusion-based sample preparation (ESP) technology at the University of Wisconsin (Madison) to isolate CTCs from patients with stage III/IV melanoma. Capture specificity of antibodies against melanoma associated proteins, NG2 (MCSP) and CD146 (MCAM) were used. We prospectively collected plasma samples from patients and evaluated the quantitative and qualitative change in numerical CTCs at baseline to 1-3 months after the start of systemic therapy. Based on CTC dynamics, a logistic regression model was used to evaluate the odds of an objective response (partial response and complete response per RECIST v1.1) and a cox proportional hazard model was used to investigate its effect on progression free survival (PFS). Results: 35 patients were evaluated and longitudinally followed. Patients were treated with immune checkpoint inhibitors (29), BRAF/MEK targeted therapy (4), or tebentafusp-tbn (2). Median follow up was 13.1 months. A range of 0 and 531 CTCs were detected at baseline (i.e. before start of treatment). Patients with an objective response had a mean slope of -22.2 CTCs/month and patients with stable disease or progressive disease had a mean slope of +10.4 CTCs/month (Wilcox p=0.0008). A qualitative decrease in CTC count was associated with an objective response (OR 6.50, 95% CI 1.80-41.57, p=0.0004) and a longer PFS (HR 0.38, 95% CI 0.15-0.91, p=0.031) compared to an increase in CTC count from baseline to 1-3 months after starting systemic therapy. Discussion: Our study demonstrates the prognostic value of CTC enumeration in advanced stage melanoma patients. Using our novel ESP technology, we are able to successfully capture CTCs and correlate CTC dynamics with clinical outcomes, including objective response and PFS. A larger sample cohort is planned to validate its utility in predicting treatment outcomes in clinical practice. Citation Format: Vincent T. Ma, Yeonhee Park, Matthew C. Mannino, Jennifer L. Schehr, Alexander Birbrair, Joshua M. Lang, George S. Zhao. Correlating circulating tumor cell dynamics with clinical outcomes in patients with advanced stage melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1984.