In Italy, since January 2022, such therapeutic combination has been approved and reimbursed only for metastatic melanoma patients with brain metastases or with PD-L1 expression <1%.<h4>Methods</h4>We conducted a real-world study in six academic centers in southern Italy and analyzed the efficacy and toxicity outcomes in 72 patients.<h4>Results</h4>The response rate was 54% (39/72) and, after 13.6 months of median follow-up, a longer median progression-free survival [17.03 months (95% CI 4.8-18.6)] compared to the pivotal CheckMate-067 trial or to other real-world studies. Here, CD274 is linked to metastatic melanoma.