Monitoring soluble cMET and ctDNA in metastatic uveal melanoma patients to track early disease progression on immunotherapies
Soluble cMET might serve as a tumor-specific biomarker to predict clinical outcomes in mUM patients.
Metastatic uveal melanoma (mUM) is a rare malignancy that differs from metastatic cutaneous melanoma in tumor characteristics and response to immunotherapies. Tumor‑specific biomarkers are required for mUM patients to monitor early disease progression on immunotherapies. We investigated clinical characteristics, including liver tumour burden and routine blood markers such as lactate dehydrogenase (LDH) and transaminases, in mUM patients treated with immune checkpoint inhibitors (ICIs) between May 2013 and February 2024. Soluble cMET (scMET) concentrations were measured by ELISA in serum samples from mUM and cutaneous melanoma cohorts, and circulating tumour DNA (ctDNA) was quantified by digital droplet PCR in mUM patients receiving ICIs or tebentafusp. scMET, ctDNA, and LDH were combined to monitor disease progression in ICI‑ and tebentafusp‑treated mUM patients. Ninety‑nine patients with mUM or liver‑metastasised cutaneous melanoma were analysed. Increased liver metastasis size (>8 cm), LDH, AST, ALT, scMET, ctDNA, and rapidly growing tumours were significantly associated with treatment resistance and shorter progression‑free and overall survival (p < 0.05). scMET (AUC = 0.82) outperformed LDH (AUC = 0.77) and S100 (0.68) for predicting one‑year overall survival in mUM patients, while scMET did not predict ICI outcomes in cutaneous melanoma cohorts. Monitoring ctDNA and scMET in mUM patients under ICIs or tebentafusp revealed the potential for early detection of disease progression.
Identifying reliable blood‑based biomarkers such as soluble cMET and ctDNA will enable clinicians to detect early disease progression in metastatic uveal melanoma patients and adjust immunotherapeutic strategies promptly, potentially improving survival outcomes.
Bizonyítékszint: Állatkísérletes. Állatmodellben vizsgálták.
Kapcsolódó jelek
- Beyond the Five-Year Milestone: Long‑term Survivorship of Melanoma Patients Treated Off‑Trial with anti‑PD‑1
- Uveal Melanoma – Trials in Disease – Overview of Information and Clinical Research
- A phase 1/2 trial of an immune-modulatory vaccine against IDO/PD-L1 in combination with nivolumab in metastatic melanoma
- Melanoma Research
- The Clinical Trial Landscape for Melanoma Therapies