Immune checkpoint inhibition in metastatic or non-resectable melanoma after failure of adjuvant anti-PD-1 treatment. A EUMelaReg real-world evidence study.

Weichenthal, MichaelEllebaek, EvaMangana, JoannaAsher, NethanelGavrilova, IvaKandolf, LidijaUgurel, SelmaHausschild, AxelMeier, FriedegundLeiter, UlrikeLivingstone, ElisabethGebhardt, ChristofferGutzmer, RalfRuhlmann, Christina HMahncke-Guldbrandt, LouiseHaslund, Charlotte AKopec, SylwiaTeterycz, PawełBender, MarcPoudroux, WilfriedMuñoz-Couselo, EvaBerciano-Guerrero, Miguel-AngelShalamanova, GerganaDePalo, Danielle KBrozic, Jasmina MaricChiarion-Sileni, VannaArance, AnnaZiogas, DimitriosRobert, Carolinevan-de-Velde, Anthonie ObikGassama, Awa AminataShapira, RonnieBenBetzalel, GuyGrynberg, ShirlyRamelyte, EgleBertoldo, FabioDelPrete, ValerioGaudy-Marqueste, CarolineMohr, PeterDummer, ReinhardAscierto, Paolo AGogas, HelenEspinosa, EnriqueLebbe, CelesteRutkowski, PiotrHaanen, JohnSchadendorf, DirkSvane, Inge Marie2025-05-282025-05-282025-03-07Weichenthal M, Ellebaek E, Mangana J, Asher N, Gavrilova I, Kandolf L, et al. Immune checkpoint inhibition in metastatic or non-resectable melanoma after failure of adjuvant anti-PD-1 treatment. A EUMelaReg real-world evidence study. Eur J Cancer. 2025 May 2;220:1153390959-8049https://hdl.handle.net/10668/28501Background: Adjuvant immune checkpoint inhibition (ICI) with anti-PD-1 antibodies in high-risk resected melanoma has been shown to improve recurrence-free survival. It is unclear whether prior adjuvant anti-PD-1 therapy is associated with altered response to subsequent ICI treatment in the metastatic setting. Methods: Using data from the European Melanoma Registry (EUMelaReg), we analyzed the efficiency of first-line (1L) ICI in non-resectable or metastatic melanoma after failure from prior adjuvant anti-PD-1 treatment. Both single-agent anti-PD-1 and combined anti-PD-1/CTLA-4 (Ipi/Nivo) 1L regimes were included in the analysis. We identified 389 patients receiving 1L ICI with prior adjuvant anti-PD-1 treatment. The control population was selected from a pool of 3390 PD-1-naive cases by 1:1 matching for the type of 1L ICI and various prognostic factors. As outcome measure, overall remission rates (ORR) were calculated and progression-free survival (PFS) was evaluated by Kaplan-Meier and Cox regression analysis. Results: Out of 389 patients, 303 (77.9 %) received Ipi/Nivo and 86 (22.1 %) anti-PD-1 in 1L. ORR was significantly lower in pre-treated patients (31.4 %) as compared to anti-PD-1 naive patients (48.8 %; p < 0.0001). Kaplan-Meier analysis showed significantly shorter median PFS for pre-treated patients. This applied to both anti-PD-1 and Ipi/Nivo treatment. Patients with early recurrence from adjuvant treatment (during or up to 12 weeks after end of treatment) showed lower ORR (28.5 %) and shorter PFS (3.1 months) than those who recurred later (37.7 % and 6.1 months, respectively). Conclusions: Patients with metastatic melanoma, previously exposed to anti-PD-1 ICI in the adjuvant setting showed significantly lower ORR and shorter PFS to 1L ICI with either Ipi/Nivo or single-agent anti-PD-1 retreatment.enAdjuvant treatmentImmunotherapyMelanomaResistanceImmune Checkpoint InhibitorsProgrammed Cell Death 1 ReceptorProgression-Free SurvivalCTLA-4 AntigenKaplan-Meier EstimatePrognosisRegression AnalysisImmune checkpoint inhibition in metastatic or non-resectable melanoma after failure of adjuvant anti-PD-1 treatment. A EUMelaReg real-world evidence study.research article40090216restricted accessPronósticoAnálisis de regresiónEstimación de Kaplan-MeierSupervivencia sin progresiónSistema de registros