The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression

Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are mainly based on clinical parameters. Recently, genomic predictors of progression have been defined f...

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Detalhes bibliográficos
Autores: Medina-Herrera, A., Vazquez, I., Cuenca, I., Rosa-Rosa, J. M., Ariceta, B., Jimenez, C., Fernandez-Mercado, M., Larrayoz, M. J., Gutierrez, N. C., Fernandez-Guijarro, M., Gonzalez-Calle, V., Rodriguez-Otero, P., Oriol, A., Rosiñol, L., Alegre, A. C., Escalante, F., de la Rubia Ortí, José Enrique, Teruel, A. I., De Arriba, F., Hernandez, M. T., Lopez-Jimenez, J., Ocio, E. M., Puig, N., Paiva, B., Lahuerta, J. J., Bladé, J., San Miguel, J. F., Mateos, M. V., Martínez López, J. I., Calasanz, M. J., Garcia-Sanz, R., GEM/PETHEM
Formato: artículo
Fecha de publicación:2024
País:España
Recursos:Universidad Católica de Valencia San Vicente Mártir
Repositorio:RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
Idioma:inglés
OAI Identifier:oai:riucv.ucv.es:20.500.12466/4459
Acesso em linha:http://hdl.handle.net/20.500.12466/4459
Access Level:acceso abierto
Palavra-chave:Smoldering multiple myeloma
Multiple myeloma
Patients
Clinical parameters
Genomic predictors
32 Ciencias Médicas
Descrição
Resumo:Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are mainly based on clinical parameters. Recently, genomic predictors of progression have been defined for untreated SMM. However, the usefulness of such markers in the context of clinical trials evaluating upfront treatment in high-risk SMM (HR SMM) has not been explored yet, precluding the identification of baseline genomic alterations leading to drug resistance. For this reason, we carried out next-generation sequencing and fluorescent in-situ hybridization studies on 57 HR and ultra-high risk (UHR) SMM patients treated in the phase II GEM-CESAR clinical trial (NCT02415413). DIS3, FAM46C, and FGFR3 mutations, as well as t(4;14) and 1q alterations, were enriched in HR SMM. TRAF3 mutations were specifically associated with UHR SMM but identified cases with improved outcomes. Importantly, novel potential predictors of treatment resistance were identified: NRAS mutations and the co-occurrence of t(4;14) plus FGFR3 mutations were associated with an increased risk of biological progression. In conclusion, we have carried out for the first time a molecular characterization of HR SMM patients treated with an intensive regimen, identifying genomic predictors of poor outcomes in this setting.

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