Recommended Dosing for Nivolumab Plus Relatlimab in Advanced Melanoma
For patients aged ≥12 years weighing ≥40 kg with unresectable or metastatic melanoma, administer nivolumab 480 mg plus relatlimab 160 mg intravenously every 4 weeks until disease progression or unacceptable toxicity. 1
Dosing Specifications
The fixed-dose combination regimen is straightforward:
- Nivolumab: 480 mg IV
- Relatlimab: 160 mg IV
- Frequency: Every 4 weeks (Q4W)
- Route: Intravenous infusion over 30 minutes
- Duration: Continue until disease progression or unacceptable toxicity 1, 2
This dosing is FDA-approved and endorsed by both ASCO 2023 guidelines and NCCN 2024 guidelines as a recommended regimen for first-line treatment of unresectable or metastatic melanoma 1.
Pediatric Considerations
For the rare pediatric patient aged ≥12 years but weighing <40 kg, weight-based dosing would theoretically apply (3 mg/kg nivolumab every 2 weeks), though the fixed-dose combination is specifically approved for patients ≥40 kg 2. In practice, most adolescents ≥12 years meet the 40 kg threshold.
Clinical Context and Evidence Base
The RELATIVITY-047 trial established this regimen's efficacy, demonstrating superior progression-free survival compared to nivolumab monotherapy (median PFS 10.1-10.2 months vs 4.6 months; HR 0.75-0.78) 1, 3, 4. With extended follow-up at 5 years, the combination continues to show durable benefit with 4-year PFS rates of 30.6% versus 23.6% for nivolumab alone 5, 6.
The combination targets two distinct immune checkpoints—PD-1 (nivolumab) and LAG-3 (relatlimab)—providing complementary mechanisms to overcome T-cell exhaustion 4. This dual blockade appears particularly effective in overcoming LAG-3-mediated resistance to PD-1 inhibition alone 5.
Safety Profile
Grade 3-4 treatment-related adverse events occur in approximately 19-22% of patients receiving the combination, compared to 10-11% with nivolumab monotherapy 3, 4. This represents a more favorable toxicity profile than nivolumab plus ipilimumab (which has ~40-50% grade 3-4 events), while maintaining comparable efficacy 7, 6.
No dose reductions are recommended for either agent—management of toxicity relies on treatment delays or permanent discontinuation per standard immune-related adverse event protocols 2.
Administration Logistics
Both agents are administered on the same day via separate infusions (if using single-agent vials) or as a fixed-dose combination product. The 30-minute infusion time applies to each agent 1, 2. Pharmacokinetic studies confirm equivalent exposures between single-agent vials given together versus the fixed-dose combination formulation 8.
Common Pitfalls to Avoid
- Do not use weight-based dosing (e.g., 3 mg/kg nivolumab) in patients ≥40 kg—the approved regimen uses fixed dosing of 480 mg nivolumab 1, 2
- Do not attempt dose reductions for toxicity management—only treatment delays or discontinuation are appropriate 2
- Do not confuse this with the nivolumab-ipilimumab regimen, which uses different dosing (nivolumab 1 mg/kg + ipilimumab 3 mg/kg every 3 weeks × 4 doses, then nivolumab maintenance) 1
The NCCN 2024 guidelines also recognize nivolumab plus relatlimab in the neoadjuvant setting (2 doses preoperatively followed by 10 adjuvant doses) as a Category 2A recommendation for resectable stage III melanoma, though this represents a distinct clinical scenario from your question about metastatic disease 7.