The clinical significance of cereblon expression in multiple myeloma

被引:91
作者
Schuster, Steven R. [1 ]
Kortuem, K. Martin [2 ]
Zhu, Yuan Xiao [2 ]
Braggio, Esteban
Shi, Chang Xin [2 ]
Bruins, Laura A. [2 ]
Schmidt, Jessica E. [2 ]
Ahmann, Greg [2 ]
Kumar, Shaji [3 ]
Rajkumar, S. Vincent [3 ]
Mikhael, Joseph [2 ]
LaPlant, Betsy
Champion, Mia D. [2 ]
Laumann, Kristina
Barlogie, Bart
Fonseca, Rafael [2 ]
Bergsagel, P. Leif [2 ]
Lacy, Martha
Stewart, A. Keith [2 ]
机构
[1] Univ Colorado Hlth, Ft Collins, CO 80524 USA
[2] Mayo Clin Arizona, Div Hematol, Scottsdale, AZ USA
[3] Mayo Clin, Div Hematol, Rochester, MN USA
关键词
Multiple myeloma; Cereblon; Gene expression profiling; Immunomodulatory drugs; Biological markers; LENALIDOMIDE; THALIDOMIDE;
D O I
10.1016/j.leukres.2013.08.015
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Cereblon (CRBN) mediates immunomodulatory drug (IMiD) action in multiple myeloma (MM). We demonstrate here that no patient with very low CRBN expression responded to IMiD plus dexamethasone therapy. In 53 refractory MM patients treated with pomalidomide and dexamethasone, CRBN levels predict for decreased response rates and significant differences in PFS (3.0 vs. 8.9 months, p<0.001) and OS (9.1 vs. 27.2 months, p=0.01) (lowest quartile vs. highest three quartiles). While higher CRBN levels can serve as a surrogate for low risk disease, our study demonstrates that low CRBN expression can predict resistance to IMiD monotherapy and is a predictive biomarker for survival outcomes. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码:23 / 28
页数:6
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