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Publications

Journal Article Ahead of print 3 citations

PubMed: 40658732 DOI: 10.1093/bjd/ljaf268

Neoadjuvant immune checkpoint inhibitors for patients with resectable stage III/IV melanoma: A nationwide real-life study in France (NEOMEL).

Br J Dermatol

Authors: Charlée Nardin, Charlotte Cavalieri, Céleste Lebbé, Emilie Gérard, Marc Puyraveau, Remi Vergara, Eve Maubec, Nora Kramkimel, Candice Lesage, Jacques Rouanet, Bertille Bonniaud, Eve Puzenat, Dragos Popescu, Barouyr Baroudjian, Yannick Le Corre, Philippe Saiag, Florence Brunet Possenti, Mélanie Saint-Jean, Henri Montaudié, Mona Amini-Adle, Samy Belkaid, Florent Grange, Sandrine Mansard, Claudia-Luisa Béjar, Sophie Darras, Cecile Pages, Emilie Tournier, Elisa Funck-Brentano, Francois Aubin

Affiliations

  • Dermatologie, Université de Franche-Comté, CHU de Besançon, INSERM, Besançon, France.
  • Dermatologie, Centre hospitalier universitaire de Besançon, Besançon, France.
  • Dermatologie, Hôpital Saint-Louis AP-HP, Paris, France.
  • Dermatologie, CHU Bordeaux, Hopital Saint André, Bordeaux, France.
  • Centre d'investigation clinique, Centre hospitalier régional universitaire de Besançon, Besançon, France.
  • Service de Pathologie, Hôpital Haut-Lévêque, CHU de Bordeaux, Université de Bordeaux, France.
  • Service de dermatologie, centre de compétence maladies génétiques à expression cutanée, Hôpital Avicenne AP-HP, Bobigny, France.
  • Dermatologie, Hôpital Cochin, AP-HP, Paris, France.
  • Soins Externes, Institut du Cancer de Montpellier - Cancer du sein - ICM/Val d'Aurelle, Montpellier, France.
  • CHU Clermont-Ferrand Site Estaing, Clermont-Ferrand, France.
  • Dermatologie, Centre Hospitalier Universitaire François Mitterand, Dijon, France.
  • Service de Dermatologie, CHU d'Angers, Angers, France.
  • Université Paris-Saclay, UVSQ, EA4340-BECCOH, Assistance Publique-Hôpitaux de Paris (AP-HP), Ambroise-Paré Hospital, Department of general and oncologic Dermatology, 92100, Boulogne-Billancourt, France.
  • Dermatologie, Hôpital Bichat - Claude-Bernard, AP-HP Université Paris Cité, Paris, France.
  • Oncologie Médicale, Institut de Cancérologie de l'Ouest (ICO), Saint-Herblain, France.
  • Service de dermatologie, Hôpital l'Archet, Nice, France.
  • Dermatologie, Centre Léon Bérard, Lyon, France.
  • Dermatologie, Hôpital Lyon Sud - HCL, Pierre-Bénite, France.
  • Dermatologie, C.H. de Valence, Valence, France.
  • Dermatologie, CHU, Clermont-Ferrand, France.
  • Dermatologie, Hôpital Avicenne AP-HP, Bobigny, France.
  • Dermatologie, C.H. Boulogne-sur-mer, Boulogne-sur-mer, France.
  • Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse, France.
  • Laboratoire d'anapath, IUCT Oncopole, Toulouse, France.

Abstract

BACKGROUND

Despite the clear therapeutic benefits of neoadjuvant treatment (NT) with immune checkpoint inhibitors (ICIs) in clinical trials, the efficacy of NT ICIs (NT-ICI) and the optimal regimen for patients (pts) with resectable metastatic melanoma (RMM) remain to be confirmed in real life.

OBJECTIVE

To assess the efficacy and safety of NT-ICI among pts with RMM in real life.

METHODS

NEOMEL is a French retrospective multicentric cohort study. Dermato-oncologists from the French group of skin cancers included pts treated with NT-ICI for RMM (AJCC 8th stage III or IV) between July 2016 and April 2024.Pts were treated either with NT anti-programmed cell death protein-1 (anti-PD-1) monotherapy or with the combination of anti-cytotoxic T lymphocyte-associated protein-4 (anti-CTLA-4) plus anti-PD-1 (1-mg/kg ipilimumab (IPI) and 3-mg/kg nivolumab (NIVO); or 3-mg/kg IPI and 1-mg/kg NIVO).The primary endpoint was the pathological complete response (pCR) rate. The secondary endpoints were pathological response according to the International Neoadjuvant Melanoma Consortium criteria, radiological response, the occurrence of immune-related adverse events (irAEs) including those of ≥ grade 3 and outcomes with recurrence-free survivals (RFS) and event-free survivals (EFS).

RESULTS

Among the 174 included pts, 149 (86%) underwent surgery. NT-ICI achieved a high pCR rate of 43% (95% CI, 34.9-51.3), including 44.7% (95% CI, 35.4-54.3) with NT-anti-PD-1 and 37.1% (95% CI, 21.5-55.1) with NT-IPI-NIVO (p=0.427). The major (complete + near-complete) pathological response rate was 53.2%. Radiological responses were observed in 49.9% of pts, including 12 complete responses (12.1%), of which 91.7% (n=11) corresponded to pCR. Severe immune-related adverse events (irAEs) occurred more frequently with NT-IPI-NIVO (24.4%) compared to NT-anti-PD-1 (3.1%) (p<0.001). The median RFS was 29.61 months (95% CI, 27.70-not reached [NR]) with significantly higher RFS in pts with pCR than no-pCR (HR, 0.218 [95% CI, 0.082-0.583], p=0.0009). The median EFS was 35.7 months 2 (95% CI, 28-NR).

CONCLUSION

In this retrospective real-life study, NT-ICI confirms its efficacy in RMM pts, achieving high pathological response rates. However, dual checkpoint inhibition with IPI-NIVO was associated with a higher risk of severe irAEs. These findings underscore the relevance of NT-ICI for RMM in clinical practice and required further confirmation.

MeSH

Syphilis, Melanoma, Drug-Related Side Effects And Adverse Reactions, Immune Checkpoint Inhibitors, Therapeutics, Dermatology