High expression of cereblon (CRBN) is associated with improved clinical response in patients with multiple myeloma treated with lenalidomide and dexamethasone

Cereblon (CRBN) has recently been identified as a target for immunomodulatory drugs (IMiDs) and its downregulation has been linked to resistance to lenalidomide. Here, we studied CRBN expression by real time polymerase chain reaction in 49 bone marrow samples of newly diagnosed patients with multiple myeloma treated with lenalidomide and dexamethasone. Median CRBN expression was 3 center dot 45 in patients who achieved complete response, and 3 center dot 75, 2 center dot 01, 0 center dot 78, and 0 center dot 70 in those with very good partial response, partial response, stable disease and progressive disease respectively. CRBN expression levels correlated significantly with response to lenalidomide treatment (r=0 center dot 48; P<0 center dot 001). Among established prognostic parameters, only beta-2-microglobulin correlated with cereblon (r=0 center dot 66; P<0 center dot 001). A close association of CRBN with interferon regulatory factor 4 (IRF4) (P<0 center dot 001) and with CTNNB1 (P<0 center dot 001) was found. Overall, a statistically significant association between baseline CRBN expression and response in MM patients treated with lenalidomide is shown. CRBN expression is closely associated with IRF4, which is an important target of IMiD therapy.