Indirect comparison of first-line nivolumab plus relatlimab or ipilimumab for advanced melanoma

First-line nivolumab plus relatlimab and first-line nivolumab plus ipilimumab have been approved for advanced melanoma on the basis of results of the phase 2-3 RELATIVITY-047 and the phase 3 CheckMate 067 trial, respectively. As no head-to-head trial comparing these regimes exist, an indirect treatment comparison was conducted using patient-level data from each trial. After IPTW, key baseline characteristics were balanced for nivolumab plus relatlimab (n=339) and nivolumab plus ipilimumab (n=297). After weighting, there were no significant differences between the two regimes for the endpoint progression-free survival or for the endpoint overall survival (A: before weighting; B: after weighting). Also the confirmed objective response rates and melanoma-specific survival were similar. Subgroup comparisons showed larger numerical differences favoring nivolumab plus ipilimumab in acral melanoma, BRAF-mutant melanoma, and LDH > 2 x upper limit of normal. Nivolumab plus relatlimab was associated with fewer grade 3 or 4 treatment-related adverse events (23% versus 61%) and fewer TRAEs leading to discontinuation (17% versus 41%). The authors conclude that nivolumab plus relatlimab demonstrated similar efficacy and improved safety to nivolumab plus ipilimumab among patients with previously untreated advanced melanoma.