Abstract 4627: Correlation of early circulating tumor DNA dynamics with whole body FDG PET/CT parameters during immune checkpoint inhibitor therapy in advanced stage melanoma

Background: Evaluation of tumor volume change and [18F]Fluoro-2-deoxy-2-D-glucose (FDG) uptake using whole-body PET/CT is frequently used to evaluate treatment response with immune checkpoint inhibitors (ICIs) in patients with advanced stage melanoma. We previously reported that early circulating tumor DNA (ctDNA) dynamics after 3-4 weeks of ICI initiation appears to be a candidate biomarker to predict treatment response. This study explores the correlation between early ctDNA dynamics and various FDG PET/CT parameters in ICI-treated patients with advanced melanoma. Methods: A prospective study was conducted for patients with unresectable stage III/IV melanoma who underwent personalized, tumor-informed ctDNA analysis (Natera) and whole-body FDG PET/CT imaging at baseline and at 3-4 weeks after treatment initiation (prior to the second dose of ICI therapy). Assessed FDG PET/CT parameters included: largest target lesion (TaL) volume, TaL SUVmax, TaL SUVmax to liver mean ratio, total lesion (ToL) SUVmax, ToL SUVmax to liver mean ratio, ToL SUVmean, and ToL SUVmean to liver ratio. Correlation coefficients were calculated to evaluate the relationship between early ctDNA dynamics and FDG PET/CT parameter changes. Results: Nine patients were evaluated, with a median age of 65 and a median baseline total number of metastatic lesions per patient of 6. Primary sites of melanoma included cutaneous (59%, 5/9), primary unknown (22%, 2/9), uveal (11%, 1/9), and mucosal (11%, 1/9). Disease stages included M1d (33%, 3/9), M1c (11%, 1/9), M1b (33%, 3/9), and M1a (22%, 2/9). Treatment regimens were split between ipilimumab/nivolumab (56%, 5/9) and nivolumab/relatlimab (44%, 4/9). All subjects with ctDNA decrease at 3-4 weeks had an overall partial response (6/9, 67%) or stable disease (1/9, 11%); and all other subjects with ctDNA increase had progressive disease (2/9, 22%) per RECIST v1.1. Strong correlations were observed between early ctDNA dynamics and changes in largest TaL volume (r = -0.9541), ToL SUVmax (r = 0.8697), and ToL SUVmax to liver mean ratio (r = 0.8414). Weak to moderate correlations were identified for other parameters. Conclusions: This study demonstrates very strong correlations between early ctDNA dynamics and several FDG PET/CT parameters, including largest TaL volume, ToL SUVmax, and ToL SUVmax to liver mean ratio. These findings highlight the potential of using ctDNA and FDG PET/CT as multifaceted early biomarkers of response to assess ICI efficacy. Ongoing patient enrollment and validation efforts are essential to establish their role in response-adapted treatment studies. Citation Format: Vincent T. Ma, Fauzia Hollnagel, Tomas A. Romero, Janmesh D. Patel, Alexander Birbrair, Robert J. Jeraj, Mark R. Albertini, Steve Y. Cho, Nandakumar Menon. Correlation of early circulating tumor DNA dynamics with whole body FDG PET/CT parameters during immune checkpoint inhibitor therapy in 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 4627.