Prospective assessment of circulating tumor DNA in patients with metastatic uveal melanoma treated with tebentafusp.
Fiche publication
Date publication
octobre 2024
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Pr KURTZ Jean-Emmanuel
Tous les auteurs :
Rodrigues M, Ramtohul T, Rampanou A, Sandoval JL, Houy A, Servois V, Mailly-Giacchetti L, Pierron G, Vincent-Salomon A, Cassoux N, Mariani P, Dutriaux C, Pracht M, Ryckewaert T, Kurtz JE, Roman-Roman S, Piperno-Neumann S, Bidard FC, Stern MH, Renault S
Lien Pubmed
Résumé
Tebentafusp, a bispecific immune therapy, is the only drug that demonstrated an overall survival benefit in patients with metastatic uveal melanoma (MUM). Circulating tumor DNA (ctDNA) has emerged as a potential prognostic and predictive marker in the phase 3 IMCgp100-202 trial using multiplex PCR-based next-generation sequencing (NGS). In this study (NCT02866149), ctDNA dynamics were assessed using droplet digital PCR (ddPCR) in 69 MUM patients undergoing tebentafusp treatment. Notably, 61% of patients exhibited detectable ctDNA before treatment initiation, which was associated with shorter overall survival (median 12.9 months versus 40.5 months for patients with undetectable ctDNA; p < 0.001). Patients manifesting a 90% or greater reduction in ctDNA levels at 12 weeks demonstrated markedly prolonged overall survival (median 21.2 months versus 12.9 months; p = 0.02). Our findings highlight the potential of ddPCR-based ctDNA monitoring as an economical, pragmatic and informative approach in MUM management, offering valuable insights into treatment response and prognosis.
Mots clés
Adult, Aged, Female, Humans, Male, Middle Aged, Biomarkers, Tumor, blood, Circulating Tumor DNA, blood, High-Throughput Nucleotide Sequencing, methods, Melanoma, genetics, Neoplasm Metastasis, Prognosis, Prospective Studies, Uveal Neoplasms, genetics
Référence
Nat Commun. 2024 10 14;15(1):8851