Expression of cereblon protein assessed by immunohistochemicalstaining in myeloma cells is associated with superior response of thalidomide- and lenalidomide-based treatment, but not bortezomib-based treatment, in patients with multiple myeloma
Journal
Annals of Hematology
Journal Volume
93
Journal Issue
8
Pages
1371-1380
Date Issued
2014
Author(s)
Lin H.-H.
Lu H.-Y.
Chou S.-J.
Abstract
Cereblon (CRBN) is essential for the anti-myeloma (MM) activity of immunomodulatory drugs (IMiDs), such as thalidomide and lenalidomide. However, the clinical implications of CRBN in MM patients are unclear. Using immunohistochemical (IHC) staining on paraffin-embedded bone marrow sections, the expression of CRBN protein in myeloma cells (MCs) was assessed in 40 relapsed/refractory MM (RRMM) patients who received lenalidomide/dexamethasone (LD) and 45 and 22 newly diagnosed MM (NDMM) patients who received thalidomide/dexamethasone (TD) and melphalan/bortezomib/prednisolone (MVP), respectively. IHC staining were scored on a scale representing the diffuseness and intensity of positive-staining MCs (range, 0-8) and a score ?4.5 was used for CRBN positivity (CRBN+) on a cut-point analysis of all possible scores and response of TD and LD. Compared to CRBN+ NDMM patients, CRBN- NDMM patients had more international staging system (ISS) III (26 vs. 61 %, respectively; P=0.006). In the LD and TD cohorts, the response rate (RR) was higher in CRBN+ patients than CRBN- patients (LD 79 vs. 33 %, respectively; P=0.005) (TD 75 vs. 29 %, respectively; P=0.005); however, this trend was not observed in the MVP cohort. In the LD and TD cohorts, the positive and negative prediction value of CRBN+ for treatment response was 79 and 67 % and 75 and 71 %, respectively. Multivariate analysis showed that CRBN+ was a significant factor associated with superior RR for LD and TD. The data suggest that expression of CRBN protein in MCs assessed using the IHC is a feasible approach to predict the response of IMiDs in MM patients. ? 2014 The Author(s).
SDGs
Other Subjects
bortezomib; cereblon; dexamethasone; lenalidomide; melphalan; prednisolone; protein derivative; thalidomide; unclassified drug; adult; aged; article; cancer prognosis; female; human; immunohistochemistry; major clinical study; male; middle aged; multiple myeloma; myeloma cell; overall survival; priority journal; progression free survival; protein expression; treatment response; Aged; Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Examination; Boronic Acids; Dexamethasone; Female; Follow-Up Studies; Gene Expression Profiling; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Neoplasm Proteins; Neoplastic Stem Cells; Paraffin Embedding; Peptide Hydrolases; Prednisolone; Pyrazines; Salvage Therapy; Survival Analysis; Syndecan-1; Thalidomide; Treatment Outcome
Publisher
Springer Verlag
Type
journal article