Prognostic Significance of Cereblon Expression in Patients With Multiple Myeloma

Clin Lymphoma Myeloma Leuk. 2016 Nov;16(11):610-615. doi: 10.1016/j.clml.2016.08.007. Epub 2016 Aug 10.

Abstract

Background: To personalize the treatment approach for patients with multiple myeloma (MM), molecular markers such as cereblon (CRBN) are currently the focus of investigation. The aim of the present study was to test the prognostic significance of CRBN expression in MM patients ineligible for autologous stem cell transplantation (ASCT).

Patients and methods: The data from 92 previously untreated patients were analyzed. The distribution according to the International Staging System score was 26.1%, 30.4%, and 43.5% with a score of 1, 2, and 3, respectively. Thalidomide- and bortezomib-based combinations were used in 83.7% and 16.3% of the patients, respectively.

Results: A treatment response (complete remission, very good partial remission, partial remission) was achieved in 83.7% of the patients and correlated with high CRBN expression (P = .006), mainly in the patients treated with thalidomide (P = .028). Low CRBN expression affected progression-free survival (PFS; P = .017) but not overall survival (OS) in patients treated with thalidomide and had no influence on OS in the bortezomib group. In the Cox regression model, low CRBN expression was the most important prognostic parameter that influenced PFS in the thalidomide-treated patients (P = .012).

Conclusion: CRBN expression is of prognostic value in MM patients ineligible for ASCT treated with thalidomide as an immunomodulatory drug. With low expression indicating a possible suboptimal treatment outcome, measurement of CRBN expression might serve as additional prognostic tool in the personalized treatment approach.

Keywords: CRBN expression; Immunomodulatory drugs; Multiple myeloma; Prognosis; Treatment.

Publication types

  • Multicenter Study

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Female
  • Gene Expression*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / mortality*
  • Multiple Myeloma / therapy
  • Neoplasm Staging
  • Peptide Hydrolases / genetics*
  • Prognosis
  • Treatment Outcome
  • Ubiquitin-Protein Ligases

Substances

  • Adaptor Proteins, Signal Transducing
  • CRBN protein, human
  • Ubiquitin-Protein Ligases
  • Peptide Hydrolases