Nivolumab/relatlimab versus nivolumab/ipilimumab for metastatic melanoma: A retrospective, propensity-matched cohort study.

Abstract

e21553 Background: Checkpoint inhibitor immunotherapy is a mainstay in the treatment of advanced melanoma. The results of the CheckMate 067 and RELATIVITY-047 trials demonstrated improved progression-free survival with dual checkpoint inhibitor therapy (ipilimumab plus nivolumab and relatlimab plus nivolumab) over nivolumab therapy alone, likely due to synergistic effect. A post hoc indirect treatment comparison using data from both trials showed an improved safety profile with relatlimab plus nivolumab over ipilimumab plus nivolumab. However, there is limited real-world data directly comparing efficacy between these two dual-checkpoint inhibitor regimens. Here, we present a retrospective database analysis comparing all-cause mortality at three years among melanoma patients treated with ipilimumab plus nivolumab versus relatlimab plus nivolumab. Methods: This global population-based retrospective cohort study was designed utilizing the TriNetX Global Collaborative network as the source of patient data and following STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines. Two patient cohorts were created using ICD-10, RxNorm, and HCPCS codes. Both cohorts consisted of patients with a diagnosis of malignant melanoma who received one of two treatments: one arm received ipilimumab with nivolumab and the other received nivolumab with relatlimab. Each cohort was prohibited from having received the treatment of the other. They were balanced by propensity score matching and the greedy nearest neighbor algorithm for age, race, gender, and ethnicity, resulting in 288 patients in each arm. The cohorts were then compared for the endpoint of mortality at 3 years. The survival endpoint of 3 years was chosen as relatlimab gained FDA approval in March 2022. Results: Treatment with nivolumab/relatlimab was associated with lower all-cause mortality at 3 years (14.9% vs 26.4%, RR 0.57, 95% CI (0.40,0.79), P value 0.0007). Conclusions: These results indicate that in the treatment of advanced melanoma with dual checkpoint inhibitor therapy, the combination of relatlimab plus nivolumab confers improved mortality at three years over ipilimumab plus nivolumab. One limitation of this study is that we were not able to control for molecular markers including PDL-1 status, mutational profile, or extent of metastatic disease. Further research including prospective studies accounting for these factors will be needed to confirm these results.