Abstract 745: Combining circulating inflammatory proteins and thymidine kinase activity to predict survival in melanoma patients receiving immune checkpoint inhibitors

Abstract Background: We have demonstrated that increased baseline levels of several inflammatory plasma proteins were associated with poorer clinical outcome in melanoma patients with metastatic cancer treated with immune checkpoint inhibitors (ICIs). Furthermore, the plasma levels and dynamics of thymidine kinase activity (TKa), which is involved in DNA synthesis and cell proliferation, have also been associated with treatment efficacy and patient outcome. The aim of our study was to explore the link between TKa, inflammation, and overall survival (OS) in ICI-treated melanoma patients. Methods: Fifty-eight patients receiving single anti-PD1 therapy for metastatic disease were treated between 2015 and 2019. There were twenty-one patients with M1a disease, fifteen patients with M1b disease, sixteen patients with M1c disease and six patients with M1d disease. TKa levels were measured with the DiviTum® TKa assay (Biovica) and correlated to 80 inflammation proteins from the Olink® target 96 inflammation platform in pretreatment plasma samples using Qlucore Omics Explorer 3.9. Results: A cut-off level of TKa at 60 Du/L has previously been determined in metastatic melanoma. Thirty-three out of 80 inflammation proteins were differentially expressed between low and high TKa groups (adjusted p-value<0.05), including IL8, CCL3, HGF and S100A12 which are also associated with shorter OS. We explored if the combination of the five unfavorable biomarkers TKa, IL8, CCL3, HGF and S100A12 could improve risk stratification for survival. When comparing Kaplan-Meier curves we observed a shorter median OS for patients with four-five or two-three markers elevated (10.2 or 18.8 months) compared with patients with one or no marker being elevated (not reached) (log-rank trend test p<0.0001). A pronounced gradual decrease in the proportion of alive patients was associated with an increasing number of unfavorable biomarkers. The five-year OS rates were 83%, 62%, 33% and 11% for the subgroup of patients with no, one, two-three or four-five elevated biomarkers, respectively. Conclusions: This multi-biomarker panel could serve as a risk stratification tool for melanoma patients to predict survival after anti-PD1 therapy. Our findings demonstrate a complex interplay between cell proliferation and pro-tumorigenic inflammation. Further investigations are warranted to elucidate the underlying biology and if circulating TKa and inflammatory proteins can be utilized jointly as biomarkers for ICI efficacy. Citation Format: Suzanne Egyhazi Brage, Fernanda Costa Svedman, Mattias Bergqvist, Hildur Helgadottir. Combining circulating inflammatory proteins and thymidine kinase activity to predict survival in melanoma patients receiving immune checkpoint inhibitors [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 745.