Differential gradients of immunotherapy vs targeted therapy efficacy according to the sun-exposure pattern of the site of occurrence of primary melanoma: a multicenter prospective cohort study (MelBase)

David Russo; Stéphane Dalle; Olivier Dereure; Laurent Mortier; Sophie Dalac-Rat; Caroline Dutriaux; Marie-Thérèse Leccia; Delphine Legoupil; Henri Montaudié; Eve Maubec; Julie De Quatrebarbes; Jean-Philippe Arnault; Florence Granel Brocard; Philippe Saïag; Brigitte Dreno; Clara Allayous; Bastien Oriano; Wendy Lefevre; Céleste Lebbé; Lise Boussemart

doi:10.3389/fonc.2023.1250026

Differential gradients of immunotherapy vs targeted therapy efficacy according to the sun-exposure pattern of the site of occurrence of primary melanoma: a multicenter prospective cohort study (MelBase)

Front Oncol. 2023 Oct 23:13:1250026. doi: 10.3389/fonc.2023.1250026. eCollection 2023.

Authors

David Russo¹, Stéphane Dalle², Olivier Dereure³, Laurent Mortier⁴, Sophie Dalac-Rat⁵, Caroline Dutriaux⁶, Marie-Thérèse Leccia^{7

8}, Delphine Legoupil⁹, Henri Montaudié¹⁰, Eve Maubec¹¹, Julie De Quatrebarbes¹², Jean-Philippe Arnault¹³, Florence Granel Brocard¹⁴, Philippe Saïag¹⁵, Brigitte Dreno¹⁶, Clara Allayous^{17

18}, Bastien Oriano¹⁷, Wendy Lefevre¹⁷, Céleste Lebbé^{17

18}, Lise Boussemart^{16

19}

Affiliations

¹ Department of Dermatology, Pontchaillou Hospital, CHU de Rennes, Rennes, France.
² Cancer Research Center of Lyon, Hospices Civils de Lyon, Pierre-Bénite, France.
³ Department of Dermatology, Hôpital Saint-Eloi, CHU de Montpellier, Montpellier, France.
⁴ Université Lille, Centre Hospitalier Régional Universitaire de Lille, Lille, France.
⁵ Dermatology Department, CHU Dijon Bourgogne, CHU Le Bocage, Dijon, France.
⁶ Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux, France.
⁷ Dermatology Department, CHU Albert Michalon, Grenoble, France.
⁸ Inserm, U1209, Université de Grenoble, Grenoble, France.
⁹ Dermatology Department, CHRU Brest, Brest, France.
¹⁰ Dermatology Department, Nice Hospital, Nice, France.
¹¹ Dermatology Department, Avicenne Hospital, AP-HP, Bobigny, France.
¹² Dermatology Department, CH d'Annecy, Pringy, France.
¹³ Dermatology Department, CHU Amiens Picardie, Amiens, France.
¹⁴ Dermatology Department, CHU de Nancy, Nancy, France.
¹⁵ Dermatology Department, Université de Versailles-Saint Quentin en Yvelines, AP-HP, Boulogne, France.
¹⁶ Nantes Université, Univ Angers, INSERM, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1302, Nantes, France.
¹⁷ AP-HP, Dermatology Department, Hôpital Saint-Louis, Paris, France.
¹⁸ Université de Paris, AP-HP Saint-Louis Hospital, Dermatology Department, INSERM U976, Paris, France.
¹⁹ Dermatology Department, CHU de Nantes, Nantes, France.

Abstract

Background: The tumor mutational burden (TMB) is high in melanomas owing to UV-induced oncogenesis. While a high TMB is a predictive biomarker of response to PD-1 inhibitors, it may be associated with the rise of resistant clones to targeted therapy over time. We hypothesized that survivals may depend on both the sun-exposure profile of the site of primary melanoma and the type of systemic treatment.

Patients and methods: Patients were screened from MelBase, a multicenter biobank dedicated to the prospective follow-up of stage III/IV melanoma. All patients with a known cutaneous primary melanoma who received a 1st-line systemic treatment by immunotherapy or targeted therapy were included (2013-2019). Outcomes were progression-free survival (PFS) and overall survival (OS).

Results: 973 patients received either anti PD-1(n=466), anti CTLA-4(n=143), a combination of both (n=118), or targeted therapies (n=246). Patients' characteristics at treatment initiation were: male (62%), median age of 62, AJCC stage IV (84%). Median follow-up was 15.5 months. The primary melanoma was located on chronically sun-exposed skin in 202 patients (G1: head neck), on intermittently sun-exposed skin in 699 patients (G2: trunk, arms, legs), and on sun-protected areas in 72 patients (G3: palms, soles). Median PFS was significantly higher in G1 under anti PD-1 treatment (8.7 months vs 3.3 and 3.4 months for G2 and G3, respectively) (p=0.011). PFS did not significantly differ in other groups. Similarly, median OS was significantly higher in G1 receiving 1^st line anti PD-1 treatment (45.6 months vs 31.6 and 21.4 months for G2 and G3) (p=0.04), as opposed to 1^st line targeted therapy (19.5 months vs 16.3 and 21.1 months for G1, G2 and G3 respectively).

Conclusion: Our study confirms that immunotherapy with anti PD-1 is particularly recommended for melanomas originating from chronically sun-exposed areas, but this finding needs to be confirmed by further research.

Keywords: UV signature; acral melanoma; immunotherapy; melanoma; sun-exposure.

Copyright © 2023 Russo, Dalle, Dereure, Mortier, Dalac-Rat, Dutriaux, Leccia, Legoupil, Montaudié, Maubec, De Quatrebarbes, Arnault, Brocard, Saïag, Dreno, Allayous, Oriano, Lefevre, Lebbé and Boussemart.