Efficacy and prognostic factors of anti-PD1 and nivolumab-ipilimumab therapy in advanced melanoma patients resistant to prior ICI treatment

Immune checkpoint inhibitors (ICIs) have significantly improved the five-year survival rate for advanced melanoma. However, many patients exhibit resistance to ICI therapy. This study evaluated the efficacy and prognostic factors of anti-PD-1 (Group A) and nivolumab-ipilimumab (Group B) therapy in patients with advanced melanoma who were resistant to prior ICI therapy. We conducted a retrospective analysis of 56 patients with advanced melanoma who had previously shown resistance to ICI therapy. In the Group A (who have previously shown resistance to anti-CTLA-4, n = 28), the objective response rate (ORR) was 42.9%, with a disease control rate (DCR) of 53%. In the Group B (previously shown resistance to anti-PD-1, n = 28), the ORR was 17.9%, and the DCR was 25%. The ORR was lower in two subgroups: patients who showed progression or relapse in the the initial radiological assessment of prior ICI therapy (ORR 10.5%) and patients who had previously received ICI in the adjuvant setting (ORR 8.3%). A Royal Marsden Hospital (RMH) score of 2-3 was a predictor of OS in both groups (Group A: HR 3.789, 95% CI 1.356-10.589, p = 0.011; Group B: HR 4.281, 95% CI 1.490-12.300, p = 0.007) and for PFS in the Group B (HR 3.167, 95% CI 1.062-9.442, p = 0.039). Anti-PD-1 therapy demonstrated efficacy following resistance to anti-CTLA-4, whereas combination ICI therapy showed lower response rates in patients resistant to anti-PD-1. Further studies are needed to confirm the RMH scores and other prognostic markers and to evaluate subgroups with lower efficacy of nivolumab-ipilimumab therapy.