Blood Test Measuring Tumor Proliferation May Guide Treatment Sequencing in Metastatic Melanoma

Metastatic melanoma remains difficult to manage because outcomes vary widely and early prognostic markers are limited. About half of patients carry a BRAF gene mutation, giving clinicians several first-line options, including targeted therapy and immunotherapy, although the optimal treatment sequence remains debated. 

Blood-based measures of tumor proliferation could support more individualized treatment selection and monitoring. New findings show that a simple blood assay of tumor cell division may help guide therapy choice in advanced melanoma.

Researchers at Karolinska Institutet assessed circulating thymidine kinase activity (TKa), a blood-based biomarker that reflects the rate of tumor cell growth and division. The team evaluated whether measuring TKa could help stratify prognosis and guide treatment selection in patients with BRAF-mutated metastatic melanoma. The study represents the first clinical trial assessment of TKa in this disease.

In the study, researchers analyzed blood samples from 81 patients with BRAF-mutated metastatic melanoma enrolled in the international SECOMBIT trial, which compared three treatment sequences combining immunotherapy and targeted therapy. Baseline TKa levels measured before treatment were evaluated in relation to clinical outcomes, while serial measurements were used to explore the biomarker’s potential for monitoring disease over time.

Patients with high pretreatment TKa experienced shorter survival and earlier disease progression than those with low levels. At five years, approximately 71% of patients with low TKa were alive compared with about 37% of those with high TKa. Treatment sequencing also appeared to differ by biomarker level: patients with high TKa seemed to benefit from a short initial course of targeted therapy before immunotherapy, whereas those with low TKa had better outcomes when immunotherapy was given first. TKa levels also tended to rise as disease progressed, suggesting potential value for monitoring treatment response over time.

The findings were published in Clinical Cancer Research on August 4, 2026. The biomarker analysis was led at Karolinska Institutet in collaboration with Biovica in Uppsala and the SECOMBIT leadership at IRCCS Fondazione G. Pascale in Naples, alongside researchers from several European universities and hospitals. Further studies are needed before the approach can be used in routine care.

“The results suggest that TKa may help identify which patients could benefit from different treatment strategies. At the same time, further studies are needed before the method can be introduced into clinical practice,” said Hildur Helgadottir, docent at the Department of Oncology-Pathology, Karolinska Institutet, and first author of the study.

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