Cereblon expression is a prognostic marker in newly diagnosed POEMS syndrome treated with lenalidomide plus dexamethasone

Ann Hematol. 2021 Jun;100(6):1547-1552. doi: 10.1007/s00277-021-04517-9. Epub 2021 Apr 10.

Abstract

POEMS syndrome is a rare plasma cell disorder. Lenalidomide has recently emerged as a therapeutic option for POEMS syndrome. Cereblon has been identified as the direct target of lenalidomide, and high cereblon expression is associated with better response and outcome to lenalidomide therapy in multiple myeloma patients. Here, we analyzed the predictive value of cereblon, IKZF1, and IKZF3 in CD138+ selected plasma cells from forty-one newly diagnosed POEMS syndrome patients treated with lenalidomide in combination with dexamethasone at both gene and protein levels. We found that patients with high cereblon expression tended to achieve better hematologic response compared to those with low expression (p = 0.024 for gene expression; p = 0.01 for protein expression). Multivariate Cox regression analysis revealed high cereblon mRNA expression as an independent prognostic marker for longer progression-free survival (hazard ratio 0.542; 95% CI 0.337-0.871; p = 0.011). In conclusion, our results emphasized the role of cereblon mRNA expression as a unique biomarker for predicting the clinical response and outcome of lenalidomide-based therapy in newly diagnosed POEMS syndrome patients.

Keywords: Cereblon; IKZF1; IKZF3; Lenalidomide; POEMS syndrome.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adult
  • Aged
  • Anti-Inflammatory Agents / therapeutic use*
  • Biomarkers, Tumor / genetics
  • Dexamethasone / therapeutic use*
  • Female
  • Gene Expression / drug effects
  • Humans
  • Immunologic Factors / therapeutic use*
  • Lenalidomide / therapeutic use*
  • Male
  • Middle Aged
  • POEMS Syndrome / diagnosis
  • POEMS Syndrome / drug therapy*
  • POEMS Syndrome / genetics
  • Prognosis
  • Prospective Studies
  • RNA, Messenger / genetics
  • Treatment Outcome
  • Ubiquitin-Protein Ligases / genetics*
  • Up-Regulation / drug effects
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • Anti-Inflammatory Agents
  • Biomarkers, Tumor
  • CRBN protein, human
  • Immunologic Factors
  • RNA, Messenger
  • Dexamethasone
  • Ubiquitin-Protein Ligases
  • Lenalidomide