and Mutation Status and Response to Checkpoint Inhibition in Advanced Melanoma.

Purpose: Little is known about the effect of specific gene mutations on efficacy of immune checkpoint inhibitors in patients with advanced melanoma.

Materials And Methods: All patients with advanced melanoma treated with first-line anti-PD-1 or ipilimumab-nivolumab between 2012 and 2021 in the nationwide Dutch Melanoma Treatment Registry were included in this cohort study. Objective response rate, progression-free survival (PFS), and overall survival (OS) were analyzed according to and status. A multivariable Cox model was used to analyze prognostic factors associated with PFS and OS.

Results: In total, 1764 patients received anti-PD-1 and 759 received ipilimumab-nivolumab. No significant differences in PFS were found in the anti-PD-1 cohort. In the ipilimumab-nivolumab cohort, median PFS was significantly higher for -mutant melanoma (9.9 months; 95% CI, 6.8 to 17.2) compared with -mutant (4.8 months; 95% CI, 3.0 to 7.5) and double wild-type (5.3 months; 95% CI, 3.6 to 7.1). In multivariable analysis, -mutant melanoma was significantly associated with a lower risk of progression or death in the ipilimumab-nivolumab cohort. Median OS was significantly higher for -mutant melanoma compared with -mutant and double wild-type melanoma for both immune checkpoint inhibitor regimens.

Conclusion: Ipilimumab-nivolumab-treated patients with -mutant melanoma display improved PFS and OS compared with patients with -mutant and double wild-type melanoma. mutation status is a factor to consider while choosing between mono and dual checkpoint inhibition in advanced melanoma.