Five-year data: adding relatlimab to nivolumab keeps a survival edge in advanced melanoma

A five-year analysis of the phase 2–3 RELATIVITY-047 trial, published in Nature Medicine on 24 October 2026, shows that combining the immunotherapies relatlimab (a LAG-3 blocker) and nivolumab (a PD-1 blocker) continues to outperform nivolumab alone in people with metastatic or unresectable melanoma.

The trial

• 714 patients were randomised 1:1 to nivolumab 480 mg plus relatlimab 160 mg (355) or nivolumab 480 mg alone (359), given intravenously every four weeks, in a double-blind design.
• Minimum follow-up in this prespecified analysis was 57.3 months.

Results

• Progression-free survival: hazard ratio 0.77 (95% CI 0.65–0.92).
• Overall survival: hazard ratio 0.78 (0.64–0.95).
• Melanoma-specific survival: hazard ratio 0.71 (0.57–0.88).
• The authors report the largest absolute differences to date between the arms, and a safety profile consistent with earlier reports.
• In biomarker work among patients with PD-L1 ≥1%, high levels of LAG-3-positive CD8 T cells were linked with worse outcomes on nivolumab alone; the authors say this supports the idea that relatlimab can overcome LAG-3-driven resistance.

Limitations

The combination is already approved on the basis of this trial; this update adds long-term data. Melanoma-specific survival and the biomarker analyses are post-hoc or exploratory, so they generate hypotheses rather than proof. Several authors are employees of Bristol Myers Squibb, which makes both drugs. The trial compared the combination with nivolumab alone, not with other combinations such as nivolumab plus ipilimumab. Patients should discuss treatment choices with their oncologist.