Markers of Efficacy to Immunotherapy in Patients With Metastatic Melanoma

Identifying Markers of Efficacy to Immunotherapy in Patients With Metastatic Melanoma: the PREMIO Study

Cutaneous melanoma is an aggressive malignancy with a rising global incidence; its prognosis has been radically transformed by immune checkpoint inhibitors (ICIs), a class of immunotherapeutic agents targeting immune regulatory pathways such as programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and lymphocyte activation gene 3 (LAG-3). Currently approved first-line treatment strategies-including anti-PD-1 monotherapy and the combinations of nivolumab plus ipilimumab and nivolumab plus relatlimab-have demonstrated significant survival benefits, although combination regimens are associated with a considerably more burdensome toxicity profile compared with monotherapy. Despite these major therapeutic advances, the optimal treatment choice for each individual patient remains uncertain, primarily due to the lack of validated predictive biomarkers in the metastatic setting. This unmet clinical need represents the central rationale of the present study, which aims to bridge this gap through the systematic collection and integrated analysis of clinical, pathological, and molecular data from approximately 200 patients treated with first-line immunotherapy at the European Institute of Oncology.

Inclusion Criteria:

• Patients with a diagnosis of metastatic or locally advanced unresectable melanoma
• Patients treated with first-line immunotherapy as monotherapy (e.g., pembrolizumab or nivolumab) or in combination (e.g., ipilimumab - nivolumab or nivolumab - relatlimab)
• Patients treated at IEO (Milan) from 01/01/2022 to 30/11/2027
• Age ≥18 years

Exclusion Criteria:

• Patients who received targeted therapy as first-line treatment for metastatic melanoma
• Patients with a diagnosis of resectable stage III melanoma or operated stage IV with no evidence of disease (NED)