Abstract

Simple SummaryImmune checkpoint inhibitors (ICI) are effective in fractions of patients with disseminated melanoma. Significant toxicity can also occur from the treatments, that, in addition, are expensive. It is therefore important to increase the knowledge of predictive factors and their efficacy in different patient groups. This study is the first to analyze the plasma activity of thymidine kinase (TK), an enzyme involved in DNA synthesis and repair, as a biomarker in melanoma patients. In this study, high TK activity (TKa) levels in melanoma patients were associated with poor baseline factors, such as poor performance status, high plasma lactate dehydrogenase levels, and advanced tumor stage. High TKa levels were also associated with a poor efficacy of immune checkpoint inhibitors. TKa is hence a novel and interesting plasma biomarker in melanoma and should be further studied to define its role as a prognostic and predictive marker in this disease.Background. Immune checkpoint inhibitors (ICI) are effective in fractions of patients with disseminated melanoma. This study is the first to analyze the plasma activity of thymidine kinase (TK), an enzyme involved in DNA synthesis and repair, as a biomarker in melanoma patients. Methods. Plasma samples were collected prior to treatment start in patients with unresectable metastatic cutaneous melanoma, treated with ICI (anti-CTLA-4 and/or anti-PD-1). Plasma TK activity (TKa) levels were determined using the DiviTum TKa ELISA assay. TKa levels were correlated with patients’ baseline characteristics, response rate (RR), progression-free survival (PFS), and overall survival (OS). Results. In the 90 study patients, the median TKa level was 42 Du/L (range <20–1787 Du/L). A significantly higher plasma TKa was found in patients with ECOG performance status ≥1 (p = 0.003), M1c-d disease (p = 0.015), and elevated lactate dehydrogenase levels (p < 0.001). The RR was 63.2% and 30.3% in those with low or high TKa, respectively (p = 0.022). The median PFS was 19.9 and 12.6 months in patients with low or high TKa, respectively (hazard ratio (HR) 1.83 (95% CI, 1.08–3.08), p = 0.024). The median OS was >60 months and 18.5 months in patients with low or high TKa, respectively (HR: 2.25 (95% CI, 1.25–4.05), p = 0.011. Conclusions. High pretreatment plasma TKa levels were significantly associated with worse baseline characteristics and poor response and survival in ICI-treated melanoma patients. TKa is hence a novel and interesting plasma biomarker in melanoma and should be further studied to define its role as a prognostic and predictive marker in this disease.

Highlights

  • In recent years, effective immune checkpoint inhibitor (ICI) regimens with CTLA-4 and Progressive disease (PD)-1 blocking antibodies have emerged for the treatment of melanoma [1,2,3,4,5,6]

  • The baseline clinical data included age at treatment start, gender, Eastern Cooperative Oncology Group (ECOG) performance status, baseline tumor stage according to the American Joint Committee (AJCC) on Cancer, Eighth Edition [16], number of affected organs, baseline lactate dehydrogenase (LDH) levels, previous lines of treatment, and ICI regime received after TKa sampling

  • A significantly higher plasma TKa was found in patients with ECOG performance status ≥1 vs. 0–1 (p = 0.003), with M1c-M1d vs. M1a-M1b disease (p = 0.015), or with elevated vs. non-elevated LDH (p < 0.001)

Read more

Summary

Introduction

Effective immune checkpoint inhibitor (ICI) regimens with CTLA-4 and PD-1 blocking antibodies have emerged for the treatment of melanoma [1,2,3,4,5,6]. TKa levels in metastatic melanoma patients were measured before starting ICI treatment and correlated with baseline clinical characteristics, treatment response, and survival. This study is the first to analyze the plasma activity of thymidine kinase (TK), an enzyme involved in DNA synthesis and repair, as a biomarker in melanoma patients. High pretreatment plasma TKa levels were significantly associated with worse baseline characteristics and poor response and survival in ICI-treated melanoma patients. TKa is a novel and interesting plasma biomarker in melanoma and should be further studied to define its role as a prognostic and predictive marker in this disease

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call