Nivolumab plus relatlimab (NIVO + RELA) fixed-dose combination did not significantly improve recurrence-free survival compared to nivolumab alone in the adjuvant treatment of completely resected stage III-IV melanoma. The combination showed higher toxicity (19% vs 8% grade 3/4 treatment-related adverse events) without clinical benefit, suggesting nivolumab monotherapy remains the preferred adjuvant approach.
Study Design & Population
- Phase 3, randomized, double-blind trial (RELATIVITY-098)
- N = 1,093 patients (547 NIVO + RELA vs 546 NIVO alone)
- Age ≥12 years with completely resected stage III-IV melanoma
- Stage distribution: 37% IIIA/B, 49% IIIC, 13% IIID/IV
- Histology: 81% cutaneous nonacral, 11% cutaneous acral, 2% mucosal
- Treatment duration: NIVO 480mg + RELA 160mg vs NIVO 480mg every 4 weeks for maximum 1 year
Key Findings
- Primary endpoint (RFS): No statistical difference between arms (specific HR not provided)
- Overall survival: Not formally tested due to hierarchical design; 148 events (48% maturity)
- Distant metastasis-free survival: Similar between groups
- Grade 3/4 TRAEs: 19% NIVO + RELA vs 8% NIVO alone
- Treatment discontinuation: 17% vs 9% due to adverse events
- Treatment-related deaths: 2 with combination vs 1 with monotherapy
Clinical Implications
- Nivolumab monotherapy remains standard adjuvant therapy for resected stage III-IV melanoma
- LAG-3 blockade addition does not provide benefit in adjuvant setting, unlike advanced disease (RELATIVITY-047)
- Risk-benefit ratio favors monotherapy due to increased toxicity without efficacy gain
- Results contrast with advanced melanoma where combination showed survival benefit
Limitations
- Biomarker analysis pending – may identify responsive subgroups
- Immature overall survival data (48% events)
- Limited follow-up (minimum 23.4 months) for long-term outcomes
- Hierarchical testing prevented formal OS analysis