Targeting the BRAF V600E Mutation in Multiple Myeloma
A partir de données portant sur 379 patients atteints d'un myélome multiple, cette étude met en évidence l'efficacité du vemurafenib chez les patients présentant la mutation V600E du gène BRAF
In multiple myeloma, there has been little progress in the specific therapeutic targeting of oncogenic mutations. Whole-genome sequencing data has recently revealed that a subset of patients carry an activating mutation (V600E) in BRAF kinase. To uncover the clinical relevance of this mutation in multiple myeloma, we correlated the mutation status in primary tumor samples from 379 myeloma patients with disease outcome. We found a significantly higher incidence of extramedullary disease and a shorter overall survival in mutation carriers when compared to controls. Most importantly, we report on a patient with confirmed BRAF V600E mutation and relapsed myeloma with extensive extramedullary disease, refractory to all approved therapeutic options, who has rapidly and durably responded to low doses of the mutation-specific BRAF inhibitor, vermurafenib. Collectively, we provide evidence for the development of the BRAF V600E mutation in the context of clonal evolution and describe a prognostic and therapeutic relevance of this targetable mutation.