The purpose of this study is to evaluate the efficacy of immunotherapy in the first-line treatment of metastatic melanoma in Slovenia and to investigate the association between PD-L1 expression and treatment response. The study aims to determine the relationship between exosomal PD-L1 miRNA expression, PD-L1 expression in tumor tissue, and PD-L1 expression on the surface of immune cells, and response to immunotherapy. The study will also evaluate the association between immune-related adverse events and survival.

This study evaluates the efficacy of immunotherapy in the first-line treatment of metastatic melanoma in Slovenia and investigates the predictive value of PD-L1 expression in tumor tissue and blood. The aim is to assess the association between exosomal PD-L1 miRNA expression, PD-L1 expression in tumor tissue, and PD-L1 expression on the surface of immune cells, and response to treatment with immune checkpoint inhibitors. In addition, the study evaluates the association between the occurrence of immune-related adverse events and survival.

Inclusion Criteria:

• Age ≥18 years
• Cytologically or histologically confirmed metastatic malignant melanoma
• Stage IIID unresectable or stage IV (AJCC 8th edition)
• ECOG performance status 0-2
• First-line systemic immunotherapy (pembrolizumab, nivolumab, or ipilimumab/nivolumab)
• CT/PET-CT performed within 4 weeks prior to treatment start
• Signed informed consent

Exclusion Criteria:

• Previous systemic therapy for melanoma
• ECOG performance status 3-4
• Contraindications to immunotherapy (immune deficiency, active immunosuppressive therapy, or active autoimmune disease requiring systemic treatment)
• Other active malignancy (except cured basal cell carcinoma, squamous cell carcinoma, or other solid tumors without recurrence >3 years)