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 journalArticle

59 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 languageEnglish (US)
Pages (from-to)23-28
Number of pages6
JournalLeukemia Research
Volume38
Issue number1
DOIs
StatePublished - 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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    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