The clinical significance of cereblon expression in multiple myeloma

Steven R. Schuster; K. Martin Kortuem; Yuan Xiao Zhu; Esteban Braggio; Chang Xin Shi; Laura A. Bruins; Jessica E. Schmidt; Greg Ahmann; Shaji Kumar; S. Vincent Rajkumar; Joseph Mikhael; Betsy LaPlant; Mia D. Champion; Kristina Laumann; Bart Barlogie; Rafael Fonseca; P. Leif Bergsagel; Martha Lacy; A. Keith Stewart

doi:10.1016/j.leukres.2013.08.015

The clinical significance of cereblon expression in multiple myeloma

Steven R. Schuster, K. Martin Kortuem, Yuan Xiao Zhu, Esteban Braggio, Chang Xin Shi, Laura A. Bruins, Jessica E. Schmidt, Greg Ahmann, Shaji Kumar, S. Vincent Rajkumar, Joseph Mikhael, Betsy LaPlant, Mia D. Champion, Kristina Laumann, Bart Barlogie, Rafael Fonseca, P. Leif Bergsagel, Martha Lacy, A. Keith Stewart

Research output: Contribution to journal › Article › peer-review

63 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	23-28
Number of pages	6
Journal	Leukemia Research
Volume	38
Issue number	1
DOIs	https://doi.org/10.1016/j.leukres.2013.08.015
State	Published - Jan 2014

Keywords

Biological markers
Cereblon
Gene expression profiling
Immunomodulatory drugs
Multiple myeloma

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

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10.1016/j.leukres.2013.08.015

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Schuster, S. R., Kortuem, K. M., Zhu, Y. X., Braggio, E., Shi, C. X., Bruins, L. A., Schmidt, J. E., Ahmann, G., Kumar, S., Rajkumar, S. V., Mikhael, J., LaPlant, B., Champion, M. D., Laumann, K., Barlogie, B., Fonseca, R., Bergsagel, P. L., Lacy, M., & Stewart, A. K. (2014). The clinical significance of cereblon expression in multiple myeloma. Leukemia Research, 38(1), 23-28. https://doi.org/10.1016/j.leukres.2013.08.015

Schuster, SR, Kortuem, KM, Zhu, YX, Braggio, E, Shi, CX, Bruins, LA, Schmidt, JE, Ahmann, G, Kumar, S , Rajkumar, SV, Mikhael, J, LaPlant, B, Champion, MD, Laumann, K, Barlogie, B, Fonseca, R , Bergsagel, PL , Lacy, M & Stewart, AK 2014, 'The clinical significance of cereblon expression in multiple myeloma', Leukemia Research, vol. 38, no. 1, pp. 23-28. https://doi.org/10.1016/j.leukres.2013.08.015

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title = "The clinical significance of cereblon expression in multiple myeloma",

abstract = "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.",

keywords = "Biological markers, Cereblon, Gene expression profiling, Immunomodulatory drugs, Multiple myeloma",

author = "Schuster, {Steven R.} and Kortuem, {K. Martin} and Zhu, {Yuan Xiao} and Esteban Braggio and Shi, {Chang Xin} and Bruins, {Laura A.} and Schmidt, {Jessica E.} and Greg Ahmann and Shaji Kumar and Rajkumar, {S. Vincent} and Joseph Mikhael and Betsy LaPlant and Champion, {Mia D.} and Kristina Laumann and Bart Barlogie and Rafael Fonseca and Bergsagel, {P. Leif} and Martha Lacy and Stewart, {A. Keith}",

note = "Funding Information: This manuscript has been funded by MMRF.",

year = "2014",

month = jan,

doi = "10.1016/j.leukres.2013.08.015",

language = "English (US)",

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pages = "23--28",

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AU - Schuster, Steven R.

AU - Kortuem, K. Martin

AU - Zhu, Yuan Xiao

AU - Braggio, Esteban

AU - Shi, Chang Xin

AU - Bruins, Laura A.

AU - Schmidt, Jessica E.

AU - Ahmann, Greg

AU - Kumar, Shaji

AU - Rajkumar, S. Vincent

AU - Mikhael, Joseph

AU - LaPlant, Betsy

AU - Champion, Mia D.

AU - Laumann, Kristina

AU - Barlogie, Bart

AU - Fonseca, Rafael

AU - Bergsagel, P. Leif

AU - Lacy, Martha

AU - Stewart, A. Keith

N1 - Funding Information: This manuscript has been funded by MMRF.

PY - 2014/1

Y1 - 2014/1

N2 - 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.

AB - 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.

KW - Biological markers

KW - Cereblon

KW - Gene expression profiling

KW - Immunomodulatory drugs

KW - Multiple myeloma

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ER -

The clinical significance of cereblon expression in multiple myeloma

Abstract

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