TY - JOUR
T1 - Neoadjuvant ipilimumab plus nivolumab in melanoma
T2 - 5-year survival and biomarker analysis from the phase 2 PRADO-trial
AU - Hoeijmakers, Lotte L.
AU - Dimitriadis, Petros
AU - Wijnen, Steven C.M.A.
AU - Reijers, Irene L.M.
AU - Lopez-Yurda, Marta
AU - Menzies, Alexander M.
AU - Broeks, Annegien
AU - Cornelissen, Sten
AU - Torres Acosta, Alejandro
AU - van der Wal, Anja
AU - Saw, Robyn P.M.
AU - Versluis, Judith M.
AU - van Houdt, Winan J.
AU - Wouters, Michel W.
AU - Romano, Jurriaan
AU - Rozeman, Eliza A.
AU - Grijpink-Ongering, Lindsay G.
AU - Kapiteijn, Ellen
AU - van der Veldt, Astrid A.M.
AU - Suijkerbuijk, Karijn P.M.
AU - Eriksson, Hanna
AU - Hospers, Geke A.P.
AU - van der Hage, Jos A.
AU - Grünhagen, Dirk J.
AU - Witkamp, Arjen J.
AU - Lijnsvelt, Judith M.
AU - Klop, Willem M.C.
AU - Zuur, Charlotte L.
AU - Bruining, Annemarie
AU - Al-Mamgani, Abrahim
AU - Pennington, Thomas E.
AU - Shannon, Kerwin F.
AU - Ch’ng, Sydney
AU - Colebatch, Andrew J.
AU - Gonzalez, Maria
AU - Spillane, Andrew J.
AU - Haanen, John B.A.G.
AU - Rawson, Robert V.
AU - Scolyer, Richard A.
AU - van de Wiel, Bart A.
AU - van Akkooi, Alexander C.J.
AU - Long, Georgina V.
AU - Blank, Christian U.
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature America, Inc. 2026.
PY - 2026/3
Y1 - 2026/3
N2 - Neoadjuvant ipilimumab plus nivolumab has become standard therapy for stage III melanoma based on the NADINA trial, although long-term data are lacking. In the phase 2 PRADO cohort of OpACIN-neo, 99 patients with stage III macroscopic melanoma received this regimen. Here we report first-time 5-year survival data: 71% event-free survival, 74% relapse-free survival, 79% distant metastasis-free survival and 86% overall survival. Ongoing grade 1−2 immune-related adverse events occurred in 69% of patients alive, predominantly vitiligo and hypothyroidism. Major pathologic response (MPR), high tumor mutational burden (TMB), high interferon-gamma (IFNγ) signature and programmed cell death ligand 1 (PD-L1) expression of 1% or higher were associated with favorable outcomes. Combined high TMB, IFNγ and PD-L1 expression yielded 100% MPR and 100% 5-year event-free survival, whereas triple low expression had only 18% MPR and 41% event-free survival. Our findings demonstrate favorable long-term outcomes for patients with an MPR and identify IFNγ and PD-L1 as promising baseline biomarkers. ClinicalTrials.gov identifier: NCT02977052.
AB - Neoadjuvant ipilimumab plus nivolumab has become standard therapy for stage III melanoma based on the NADINA trial, although long-term data are lacking. In the phase 2 PRADO cohort of OpACIN-neo, 99 patients with stage III macroscopic melanoma received this regimen. Here we report first-time 5-year survival data: 71% event-free survival, 74% relapse-free survival, 79% distant metastasis-free survival and 86% overall survival. Ongoing grade 1−2 immune-related adverse events occurred in 69% of patients alive, predominantly vitiligo and hypothyroidism. Major pathologic response (MPR), high tumor mutational burden (TMB), high interferon-gamma (IFNγ) signature and programmed cell death ligand 1 (PD-L1) expression of 1% or higher were associated with favorable outcomes. Combined high TMB, IFNγ and PD-L1 expression yielded 100% MPR and 100% 5-year event-free survival, whereas triple low expression had only 18% MPR and 41% event-free survival. Our findings demonstrate favorable long-term outcomes for patients with an MPR and identify IFNγ and PD-L1 as promising baseline biomarkers. ClinicalTrials.gov identifier: NCT02977052.
UR - https://www.scopus.com/pages/publications/105028900056
U2 - 10.1038/s41591-025-04158-9
DO - 10.1038/s41591-025-04158-9
M3 - Article
C2 - 41606118
AN - SCOPUS:105028900056
SN - 1078-8956
VL - 32
SP - 952
EP - 963
JO - Nature medicine
JF - Nature medicine
IS - 3
ER -
SDG 3 Good Health and Well-being