Journal: Nature medicine
This phase 2 PRADO cohort of the OpACIN-neo study reports 5‑year outcomes for 99 patients with stage III macroscopic melanoma treated with neoadjuvant ipilimumab plus nivolumab.
Key efficacy findings (5-year estimates):
- Event-free survival: 71%
- Relapse-free survival: 74%
- Distant metastasis–free survival: 79%
- Overall survival: 86%
Toxicity:
- Persistent grade 1–2 immune-related adverse events in 69% of surviving patients, mainly vitiligo and hypothyroidism; no higher-grade late toxicities are described in the abstract.
Biomarkers and response:
- Major pathologic response (MPR) was strongly associated with favorable long-term outcomes.
- High tumor mutational burden (TMB), high interferon-gamma (IFNγ) gene signature, and PD-L1 expression ≥1% each correlated with better outcomes.
- Patients with all three biomarkers “high” had:
- 100% MPR rate
- 100% 5-year event-free survival
- Patients with all three biomarkers “low” had:
- 18% MPR rate
- 41% 5-year event-free survival
Clinical implications:
- Neoadjuvant ipilimumab plus nivolumab yields durable long-term control in stage III melanoma, especially in those achieving MPR.
- Baseline IFNγ signature and PD-L1, together with TMB, emerge as promising predictors of deep pathologic response and long-term benefit.