Abstract 1133P
Background
Cutaneous melanomas have a high tumor mutational burden (TMB) because of mutations induced by ultraviolet radiations (UVR). TMB is a predictive biomarker of response to PD-1 inhibitors but it is unfortunately not yet routinely available. Considering photoaging 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. Five independent dermatologists assessed the grade of photoaging for each patient using two clinical scales, one descriptive and the second photo-analogic (McKenzie Photographic Scale), in a blinded, photographic assessment. The reliability of the clinical scales was statistically assessed by intraclass correlation coefficients (ICC). 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, <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).
Conclusions
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.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Boussemart Lise.
Funding
Has not received any funding.
Disclosure
T. Lesimple: Research grant/Funding (self): Roche; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Pierre Fabre; Travel/Accommodation/Expenses: MSD. L. Boussemart: Advisory/Consultancy: Novartis; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Roche; Advisory/Consultancy: BMS; Advisory/Consultancy: MSD. All other authors have declared no conflicts of interest.