| Autor: |
Rozeman, E.A., Hoefsmit, E.P., Reijers, I.L.M., Saw, R.P.M., Versluis, J.M., Krijgsman, O., Dimitriadis, P., Sikorska, K., Wiel, B.A. van de, Eriksson, H., Gonzalez, M., Acosta, A.T., Grijpink-Ongering, L.G., Shannon, K., Haanen, J.B.A.G., Stretch, J., Ch'ng, S., Nieweg, O.E., Mallo, H.A., Adriaansz, S., Kerkhoven, R.M., Cornelissen, S., Broeks, A., Klop, W.M.C., Zuur, C.L., Houdt, W.J. van, Peeper, D.S., Spillane, A.J., Akkooi, A.C.J. van, Scolyer, R.A., Schumacher, T.N.M., Menzies, A.M., Long, G.V., Blank, C.U. |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
Nature medicine. 27(2) |
| ISSN: |
1546-170X |
| Popis: |
Neoadjuvant ipilimumab plus nivolumab showed high pathologic response rates (pRRs) in patients with macroscopic stage III melanoma in the phase 1b OpACIN () and phase 2 OpACIN-neo () studies(1,2). While the results are promising, data on the durability of these pathologic responses and baseline biomarkers for response and survival were lacking. After a median follow-up of 4 years, none of the patients with a pathologic response (n = 7/9 patients) in the OpACIN study had relapsed. In OpACIN-neo (n = 86), the 2-year estimated relapse-free survival was 84% for all patients, 97% for patients achieving a pathologic response and 36% for nonresponders (P < 0.001). High tumor mutational burden (TMB) and high interferon-gamma-related gene expression signature score (IFN-gamma score) were associated with pathologic response and low risk of relapse; pRR was 100% in patients with high IFN-gamma score/high TMB; patients with high IFN-gamma score/low TMB or low IFN-gamma score/high TMB had pRRs of 91% and 88%; while patients with low IFN-gamma score/low TMB had a pRR of only 39%. These data demonstrate long-term benefit in patients with a pathologic response and show the predictive potential of TMB and IFN-gamma score. Our findings provide a strong rationale for a randomized phase 3 study comparing neoadjuvant ipilimumab plus nivolumab versus standard adjuvant therapy with antibodies against the programmed cell death protein-1 (anti-PD-1) in macroscopic stage III melanoma. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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