Cereblon gene expression and correlation with clinical outcomes in patients with relapsed/refractory multiple myeloma treated with pomalidomide: an analysis of STRATUS

Leuk Lymphoma. 2019 Feb;60(2):462-470. doi: 10.1080/10428194.2018.1485915. Epub 2018 Aug 2.

Abstract

We analyzed gene expression levels of CRBN, cMYC, IRF4, BLIMP1, and XBP1 in 224 patients with multiple myeloma treated with pomalidomide and low-dose dexamethasone in the STRATUS study (ClinicalTrials.gov: NCT01712789; EudraCT number: 2012-001888-78). Clinical responses were observed at all CRBN expression levels. A trend in progression-free survival (PFS; p = .038) and a potential trend in overall survival (OS; p = .059) favoring high CRBN expressers were observed; however, no notable difference in overall response rate (ORR) was observed. ORR (30%), median PFS (17.7 weeks), and median OS (52.3 weeks) in low-CRBN expressers were comparable to those in the STRATUS intent-to-treat population (ORR, 33%; median PFS, 20.0 weeks; median OS, 51.7 weeks). A trend in ORR (p = .050) favoring higher cMYC expressers was observed with no notable difference in PFS or OS. This analysis does not support exploring CRBN as a biomarker for selecting patients for pomalidomide therapy.

Keywords: Multiple myeloma; biomarker; cereblon; immunomodulatory agent; pomalidomide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor*
  • Computational Biology / methods
  • Drug Resistance, Neoplasm
  • Female
  • Gene Expression Profiling
  • Gene Expression*
  • Humans
  • Immunologic Factors / therapeutic use
  • Male
  • Middle Aged
  • Molecular Sequence Annotation
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / mortality*
  • Multiple Myeloma / therapy
  • Neoplasm Staging
  • Prognosis
  • Recurrence
  • Retreatment
  • Thalidomide / analogs & derivatives
  • Thalidomide / therapeutic use
  • Treatment Outcome
  • Ubiquitin-Protein Ligases

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • CRBN protein, human
  • Immunologic Factors
  • Thalidomide
  • pomalidomide
  • Ubiquitin-Protein Ligases

Associated data

  • ClinicalTrials.gov/NCT01712789