Abstract
Combination therapy with nivolumab and ipilimumab (NIVO+IPI) is highly effective in treating advanced malignant melanoma (MM) but it is associated with a high incidence of treatment-related adverse events (TRAEs). This retrospective, cohort study evaluated the efficacy and TRAEs of NIVO+IPI in Japanese patients with unresectable stage III and IV MM, comparing outcomes based on the number of treatment cycles and the IPI dose. We reviewed data from 57 patients with advanced or recurrent MM who received NIVO+IPI at the Shizuoka Cancer Center between August 2015 and July 2024. Patients who received two or fewer NIVO + IPI cycles (NIVO+IPI ≤2 cycles) generally had worse Eastern Cooperative Oncology Group performance status and more advanced stages compared to those who received three or more cycles (NIVO+IPI ≥3 cycles). The analysis revealed that the NIVO+IPI ≥3 cycles group had significantly better overall survival compared to the NIVO+IPI ≤2 cycles group, although receiving three or more cycles was not an independent prognostic factor in multivariate analysis. There was no significant difference in the frequency or severity of TRAEs between the two groups, but the incidence of grade ≥3 TRAEs increased significantly between the first and second cycles of NIVO+IPI. Additionally, reducing the IPI dose from 3 mg/kg to 2 mg/kg appeared to lower the risk of grade ≥3 TRAEs. In conclusion, further research is needed to determine the optimal number of NIVO+IPI cycles for Japanese patients with advanced MM. However, assessing efficacy after the second cycle may help avoid unnecessary NIVO+IPI administration. Reducing the IPI dose to 2 mg/kg may also offer a safer treatment approach for these patients.