Portal de investigación
The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression.
Fecha de publicación:
Fecha Ahead of Print:
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Medina-Herrera A
- Vazquez I
- Cuenca I
- Rosa-Rosa JM
- Ariceta B
- Jimenez C
- Fernandez-Mercado M
- Larrayoz MJ
- Gutierrez NC
- Fernandez-Guijarro M
- Gonzalez-Calle V
- Rodriguez-Otero P
- Oriol A
- Rosiñol L
- Alegre A
- Escalante F
- Teruel AI
- De Arriba F
- Hernandez MT
- Lopez-Jimenez J
- Ocio EM
- Puig N
- Paiva B
- Lahuerta JJ
- Bladé J
- San Miguel JF
- Mateos MV
- Martinez-Lopez J
- Calasanz MJ
- Garcia-Sanz R
- GEM/PETHEMA (Grupo Español de Mieloma/Programa para el Estudio de la Terapéutica
Grupos
Abstract
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.
© 2024. The Author(s).
Datos de la publicación
- ISSN/ISSNe:
- 2044-5385, 2044-5385
- Tipo:
- Article
- Páginas:
- 74-74
- PubMed:
- 38684670
- Factor de Impacto:
- 3,221 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
Blood Cancer Journal SPRINGERNATURE
Citas Recibidas en Web of Science: 10
Documentos
- No hay documentos
Filiaciones
Keywords
- TERM-FOLLOW-UP; MULTIPLE-MYELOMA; MUTATIONS; CRITERIA; CONSENSUS
Campos de Estudio
Cita
Medina A,Vazquez I,Cuenca I,Rosa JM,Ariceta B,Jimenez C,Fernandez M,Larrayoz MJ,Gutierrez NC,Fernandez M,Gonzalez V,Rodriguez P,Oriol A,Rosiñol L,Alegre A,Escalante F,DE LA RUBIA J,Teruel AI,De Arriba F,Hernandez MT,Lopez J,Ocio EM,Puig N,Paiva B,Lahuerta JJ,Bladé J,San Miguel JF,Mateos MV,Martinez J,Calasanz MJ,Garcia R,GEM/PETHEMA (Grupo Español de Mieloma/Programa para el Estudio de la T. The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression. Blood Cancer J. 2024. 14. (1):p. 74-74. IF:11,600. (1).