Prospective assessment of circulating tumor DNA in patients with metastatic uveal melanoma treated with tebentafusp
Manuel Rodrigues, Toulsie Ramtohul, Aurore Rampanou, José Luis Ruiz Sandoval, Alexandre Houy, Vincent Servois, Léah Mailly-Giacchetti, Gaëlle Pierron, Anne Vincent‐Salomon, Nathalie Cassoux, Pascale Mariani, Caroline Dutriaux, Marc Pracht, Thomas Ryckewaert, Jean‐Emmanuel Kurtz, Sergio Roman‐Roman, Sophie Piperno‐Neumann, François‐Clément Bidard, Marc‐Henri Stern, Shufang Renault
Abstract
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.