The clinical significance of cereblon expression in multiple myeloma

Leuk Res. 2014 Jan;38(1):23-8. doi: 10.1016/j.leukres.2013.08.015. Epub 2013 Sep 5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / genetics
  • Cell Line, Tumor
  • Dexamethasone / administration & dosage
  • Drug Resistance, Neoplasm / genetics
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / pathology
  • Peptide Hydrolases / genetics*
  • Prognosis
  • Survival Analysis
  • Thalidomide / administration & dosage
  • Thalidomide / analogs & derivatives
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • CRBN protein, human
  • Thalidomide
  • Dexamethasone
  • pomalidomide
  • Peptide Hydrolases