Clinical activity and safety of nivolumab in combination with ipilimumab in metastatic melanoma: findings from REALIPINIVO, a real-world study

Introduction: Metastatic melanoma has historically had a poor prognosis; however, survival has improved with immunotherapies, such as PD-1 and CTLA-4 inhibitors, and molecular targeted therapies for BRAF-mutant tumors. The combination of nivolumab and ipilimumab is highly effective, though with increased rates of toxicity. 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%. Methods: We conducted a real-world study in six academic centers in southern Italy and analyzed the efficacy and toxicity outcomes in 72 patients. Results: 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. Better survival correlated with objective responses (p<0.0001) and low disease burden (less than three metastatic sites) (p=0.0415). All patients achieving an objective response had tumors with high or intermediatetumor mutational burden. The rates of immune-related adverse events were similar to those reported in the literature, but there was a lower therapy discontinuation rate. This might be due to more appropriate managing of emerging immunotherapy toxicities.