Immune-Related and Cutaneous Adverse Events Associated with Relatlimab Mono/Combo Regimens Versus Other Immune Checkpoint Inhibitors in Advanced, Non-Resectable Cutaneous Melanoma: Systematic Review and Meta-Analysis

Abstract

Specific Aims: The RELATIVITY-047 trial showcased relatlimab's effectiveness alongside nivolumab for advanced non-resectable cutaneous melanoma. This systematic review and meta-analysis in progress aims to evaluate relatlimab's safety as monotherapy or combined with nivolumab, compared to other immune checkpoint inhibitors, regarding cutaneous and immune-related adverse events, including grade 3/4 dermatological adverse events. Methods: In pairs, four independent reviewers will search databases for reports on advanced non-resectable cutaneous melanoma treatments with immune checkpoint inhibitors (ICIs). Exclusions encompass uveal, mucosal, and bronchial melanoma, patients with resected melanoma, autoimmune diseases, or aged<18. Data extraction includes study details, adverse events, and interventions. Disagreements will be resolved through discussion or escalated to a fifth reviewer. Meta-analyses will estimate relatlimab's adverse event frequency and risk compared to other ICIs, utilizing random-effect models and the Freeman-Tukey double arcsine transformation. Heterogeneity will be assessed using the I2 statistic, with subgroup analyses planned for high heterogeneity cases where I2>75%. The Cochrane Collaboration Risk of Bias Assessment Tool for randomized trials and the Newcastle-Ottawa Scale for nonrandomized studies will evaluate risk of bias. Results: 1339 studies have been included for full-text screening, of which, 7.6% are randomized controlled trials, 0.2% case series, 21.0% retrospective studies, and 5.7% prospective studies. The remaining 65.5% of studies are expected to be excluded. Conclusions: Preliminary findings of this systematic review highlight the diverse literature on safety profiles of established ICIs for melanoma treatment. This underscores the need for comparative safety data on relatlimab.