Prospective assessment of circulating tumor DNA in patients with metastatic uveal melanoma treated with tebentafusp
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 multip...
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Nature Portfolio
2024-10-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-53145-0 |
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| author | Manuel Rodrigues Toulsie Ramtohul Aurore Rampanou José Luis Sandoval Alexandre Houy Vincent Servois Léah Mailly-Giacchetti Gaelle 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 |
| author_facet | Manuel Rodrigues Toulsie Ramtohul Aurore Rampanou José Luis Sandoval Alexandre Houy Vincent Servois Léah Mailly-Giacchetti Gaelle 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 |
| author_sort | Manuel Rodrigues |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7a7c81a35eee4eb6a90455852698d2be |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-7a7c81a35eee4eb6a90455852698d2be2025-08-20T02:17:50ZengNature PortfolioNature Communications2041-17232024-10-0115111010.1038/s41467-024-53145-0Prospective assessment of circulating tumor DNA in patients with metastatic uveal melanoma treated with tebentafuspManuel Rodrigues0Toulsie Ramtohul1Aurore Rampanou2José Luis Sandoval3Alexandre Houy4Vincent Servois5Léah Mailly-Giacchetti6Gaelle Pierron7Anne Vincent-Salomon8Nathalie Cassoux9Pascale Mariani10Caroline Dutriaux11Marc Pracht12Thomas Ryckewaert13Jean-Emmanuel Kurtz14Sergio Roman-Roman15Sophie Piperno-Neumann16François-Clément Bidard17Marc-Henri Stern18Shufang Renault19Department of Medical Oncology, Institut CurieDepartment of Radiology, Institut Curie, PSL Research UniversityCirculating Tumor Biomarkers Laboratory, Inserm CIC-BT 1428, Department of Translational Research, Institut CurieCirculating Tumor Biomarkers Laboratory, Inserm CIC-BT 1428, Department of Translational Research, Institut CurieInserm U830, DNA Repair and Uveal Melanoma (D.R.U.M.) team, Institut Curie, PSL Research UniversityDepartment of Radiology, Institut Curie, PSL Research UniversityInserm U830, DNA Repair and Uveal Melanoma (D.R.U.M.) team, Institut Curie, PSL Research UniversitySomatic Genetic Unit, Department of Genetics, Institut Curie, PSL Research UniversityDepartment of Pathology, Institut Curie, PSL Research UniversityDepartment of Surgical Oncology, Institut Curie, PSL Research UniversityDepartment of Surgical Oncology, Institut Curie, PSL Research UniversityDermatology Department, Hôpital Saint André Centre Hospitalier UniversitaireMedical Oncology Department, Centre Eugène MarquisMedical Oncology Department, Oscar Lambret CenterDepartment of Medical and Surgical Oncology & Hematology, ICANSInserm U830, DNA Repair and Uveal Melanoma (D.R.U.M.) team, Institut Curie, PSL Research UniversityDepartment of Medical Oncology, Institut CurieDepartment of Medical Oncology, Institut CurieInserm U830, DNA Repair and Uveal Melanoma (D.R.U.M.) team, Institut Curie, PSL Research UniversityCirculating Tumor Biomarkers Laboratory, Inserm CIC-BT 1428, Department of Translational Research, Institut CurieAbstract 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.https://doi.org/10.1038/s41467-024-53145-0 |
| spellingShingle | Manuel Rodrigues Toulsie Ramtohul Aurore Rampanou José Luis Sandoval Alexandre Houy Vincent Servois Léah Mailly-Giacchetti Gaelle 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 Prospective assessment of circulating tumor DNA in patients with metastatic uveal melanoma treated with tebentafusp Nature Communications |
| title | Prospective assessment of circulating tumor DNA in patients with metastatic uveal melanoma treated with tebentafusp |
| title_full | Prospective assessment of circulating tumor DNA in patients with metastatic uveal melanoma treated with tebentafusp |
| title_fullStr | Prospective assessment of circulating tumor DNA in patients with metastatic uveal melanoma treated with tebentafusp |
| title_full_unstemmed | Prospective assessment of circulating tumor DNA in patients with metastatic uveal melanoma treated with tebentafusp |
| title_short | Prospective assessment of circulating tumor DNA in patients with metastatic uveal melanoma treated with tebentafusp |
| title_sort | prospective assessment of circulating tumor dna in patients with metastatic uveal melanoma treated with tebentafusp |
| url | https://doi.org/10.1038/s41467-024-53145-0 |
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