Abstract
BACKGROUND: Inflammatory plasma proteins have been associated with poorer clinical outcomes in melanoma patients treated with immune checkpoint inhibitors (ICIs). Furthermore, the plasma levels of thymidine kinase activity (TKa), an indicator of proliferation, have also been associated with adverse outcomes in several cancers. The aim of this study was to explore the relationship between TKa, systemic inflammation and survival in ICI-treated melanoma patients. MATERIALS AND METHODS: Fifty-eight patients with unresectable metastatic melanoma who received anti-programmed cell death protein 1 monotherapy were included in the study. Pretreatment plasma samples were analyzed for TKa levels (DiviTum® TKa assay; Biovica) and inflammatory proteins using the Olink® Target 96 Inflammation panel, and these biomarkers were correlated with patient survival. RESULTS: A panel of five unfavorable biomarkers was selected, comprising TKa, C-X-C motif chemokine ligand 8, C-C motif chemokine ligand 3, hepatocyte growth factor and S100 calcium-binding protein A12. An increasing number of elevated biomarkers in the panel was associated with a progressively worse prognosis. In the univariate analysis, when patients with four to five unfavorable biomarkers were compared with those with none, the hazard ratio (HR) was 2.43 [95% confidence interval (CI) 0.91-6.44, P = 0.075] for progression-free survival (PFS) and 10.62 (95% CI 3.11-36.26, P < 0.001) for overall survival (OS). When adjusting for sex, age, stage and lactate dehydrogenase (LDH), the HR was 1.97 (95% CI 0.61-6.41, P = 0.26) for PFS and 11.03 (95% CI 2.53-48.12, P = 0.001) for OS. CONCLUSION: This multi-biomarker panel was independently associated with poor OS in ICI-treated melanoma patients. This finding suggests a prognostic value of the panel, indicating its potential relevance for stratifying patients by risk, although further validation in larger cohorts is warranted.