Prospective assessment of circulating tumor DNA in patients with metastatic uveal melanoma treated with tebentafusp
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.
Authors
- Toulsie Ramtohul (ORCID: https://orcid.org/0000-0002-8440-7785)
- Sophie Piperno‐Neumann (ORCID: https://orcid.org/0000-0001-9915-2810)
- François‐Clément Bidard (ORCID: https://orcid.org/0000-0001-5932-8949)
- Aurore Rampanou (ORCID: https://orcid.org/0009-0004-2154-6376)
- Nathalie Cassoux (ORCID: https://orcid.org/0000-0002-5535-9649)
- Vincent Servois (ORCID: https://orcid.org/0000-0002-8378-8432)
- Pascale Mariani (ORCID: https://orcid.org/0000-0003-2648-0367)
- Thomas Ryckewaert
- Marc Pracht (ORCID: https://orcid.org/0000-0001-8110-0780)
- Marc‐Henri Stern (ORCID: https://orcid.org/0000-0002-8100-2272)
- Anne Vincent‐Salomon (ORCID: https://orcid.org/0000-0001-5754-5771)
- Alexandre Houy (ORCID: https://orcid.org/0000-0001-6267-2353)
- Manuel Rodrigues (ORCID: https://orcid.org/0000-0002-5443-0802)
- Léah Mailly-Giacchetti
- Caroline Dutriaux (ORCID: https://orcid.org/0000-0002-9836-5168)
- Shufang Renault (ORCID: https://orcid.org/0000-0001-9234-1002)
- Sergio Roman‐Roman (ORCID: https://orcid.org/0000-0001-6459-2613)
- Gaëlle Pierron (ORCID: https://orcid.org/0000-0002-2536-7680)
- Jean‐Emmanuel Kurtz (ORCID: https://orcid.org/0000-0003-4611-5797)
- José Luis Ruiz Sandoval
Institutions
- Inserm (FR)
- Université de Versailles Saint-Quentin-en-Yvelines (FR)
- Université Paris Sciences et Lettres (FR)
- Université Paris-Saclay (FR)
- Institut de Cancérologie Strasbourg (FR)
- Centre Eugène Marquis (FR)
- Hôpital Saint-André (FR)
- Centre Oscar Lambret (FR)
- Institut Curie (FR)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-10-14
- DOI
- https://doi.org/10.1038/s41467-024-53145-0
- Citations
- 23
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 6.56
Funders
- Institut National de la Santé et de la Recherche Médicale
- Institut National Du Cancer
- Direction Générale de l’offre de Soins