Neoadjuvant Nivo + Relatlimab (PD-1 / LAG-3) Yields 80% 4-Year EFS in Resectable Stage III-IV Melanoma

Relatlimab (anti-LAG-3) plus nivolumab (anti-PD-1) was given peri-operatively in the single-arm Phase II NCT02519322 study. Thirty patients with resectable stage III/IV melanoma received two neoadjuvant doses, surgery, then ten adjuvant cycles. Major pathologic response was 63%. After a median 47 mo follow-up, 4-year event-free survival reached 80%, climbing to 95% in patients who achieved MPR. No grade ≥3 immune-related AEs were seen during the neoadjuvant window, and <10% discontinued adjuvant dosing for toxicity. This long-term EFS outperforms historical adjuvant nivolumab alone (4-yr RFS ≈ 52% in CheckMate-238) and tops the 2-yr 72% EFS reported for neoadjuvant–adjuvant pembrolizumab in SWOG S1801, with a safety profile that is better than Ipi/Nivo Baseline IFN-γ–driven signatures correlated with response, whereas high B7-H3 expression flagged resistance.