Skin photoaging around the site of occurrence of primary melanoma as a clinical predictive biomarker of response to PD-1 inhibitors

Purpose. - Cutaneous melanomas have a high tumor mutational burden (TMB) because of mutations induced by ultraviolet radiations. TMB is a predictive biomarker of response to PD-1 inhibitors but it is unfortunately not yet routinely available. Considering dermatoheliosis as a result of repeated and cumulative exposure to UVR, we hypothesized that signs of photoaging around primary melanoma could predict response to PD-1 inhibitors. Methods. - We conducted a retrospective bicentric study including 34 patients with stage IV melanoma treated with first-line immunotherapy. Dermatoheliosis was assessed by varios clinical scales. Outcomes were progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Results. - The clinical scales, graded from 0 to 3, were reproducible, with an ICC of 0.68 for the descriptive scale and 0.72 for the photo-analogic scale. PFS was significantly higher in case of severe photoaging with both the descriptive scale and the photo-analogic scale (HR = 0.32, P < 10(-3), and HR = 0.41, P < 10(-3), respectively). Similarly, OS was higher when photoaging was assessed severe. Three-month ORR was better in cases of severe photoaging than in cases of mild/no photoaging, both with the descriptive and photo-analogic scales (77 vs. 24% and 61 vs. 25% respectively). Conclusion. - Our study suggests that reliable determination of photoaging around a melanoma or its scar can be used as a predictive clinical biomarker of response to PD-1 inhibitors, higher grades being associated with better response rate and progression-free survival. (c) 2023 l'Academie nationale de medecine. Published by Elsevier Masson SAS. All rights reserved.