Background:
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.

Source:

Weichenthal, M., Ellebaek, E., Mangana, J., Asher, N., Gavrilova, I., Kandolf, L., Ugurel, S., Hausschild, A., Meier, F., Leiter, U., Livingstone, E., Gebhardt, C., Gutzmer, R., Ruhlmann, C. H., Mahncke-Guldbrandt, L., Haslund, C. A., Kopec, S., Teterycz, P., Bender, M., … Svane, I. M. (2025). Immune checkpoint inhibition in metastatic or non-resectable melanoma after failure of adjuvant anti-PD-1 treatment. A EUMELAREG real-world evidence study. European Journal of Cancer, 220, 115339. https://doi.org/10.1016/j.ejca.2025.115339

https://www.ejcancer.com/article/S0959-8049(25)00120-0/fulltext