Targeting the BRAF V600E Mutation in Multiple Myeloma

被引：193

作者：

Andrulis, Mindaugas ^{[1
]}

Lehners, Nicola ^{[2
,3
,4
]}

Capper, David ^{[5
,6
]}

Penzel, Roland ^{[2
]}

Heining, Christoph ^{[7
]}

Huellein, Jennifer ^{[7
]}

Zenz, Thorsten ^{[2
,7
]}

von Deimling, Andreas ^{[5
,6
]}

Schirmacher, Peter ^{[1
]}

Ho, Anthony D. ^{[2
]}

Goldschmidt, Hartmut ^{[2
,8
]}

Neben, Kai ^{[2
]}

Raab, Marc S. ^{[2
,3
,4
]}

机构：

[1] Heidelberg Univ, Inst Pathol, Dept Gen Pathol, Heidelberg, Germany

[2] Univ Heidelberg Hosp, Dept Med 5, D-69120 Heidelberg, Germany

[3] German Canc Res Ctr, Max Eder Grp Expt Therapies Hematol Malignancies, Heidelberg, Germany

[4] Heidelberg Univ, Heidelberg, Germany

[5] Heidelberg Univ, Inst Pathol, Dept Neuropathol, Heidelberg, Germany

[6] German Canc Res Ctr, Clin Cooperat Unit Neuropathol, Heidelberg, Germany

[7] Natl Ctr Tumor Dis NCT, Dept Translat Oncol, Heidelberg, Germany

[8] Natl Ctr Tumor Dis NCT, Dept Med Oncol, Heidelberg, Germany

来源：

CANCER DISCOVERY | 2013年 / 3卷 / 08期

关键词：

IMPROVED SURVIVAL; RAF INHIBITION; MELANOMA; DABRAFENIB; RESISTANCE; IMATINIB;

D O I：

10.1158/2159-8290.CD-13-0014

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

In multiple myeloma, there has been little progress in the specific therapeutic targeting of oncogenic mutations. Whole-genome sequencing data have recently revealed that a subset of patients carry an activating mutation (V600E) in the BRAF kinase. To uncover the clinical relevance of this mutation in multiple myeloma, we correlated the mutation status in primary tumor samples from 379 patients with myeloma with disease outcome. We found a significantly higher incidence of extramedullary disease and a shorter overall survival in mutation carriers when compared with 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 the prognostic and therapeutic relevance of this targetable mutation. (C) 2013 AACR.

引用

页码：862 / 869

页数：8

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