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Multicenter Study
. 2013 Jun;161(5):695-700.
doi: 10.1111/bjh.12338. Epub 2013 Apr 9.

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

Daniel Heintel  1 , Alberto Rocci  2 , Heinz Ludwig  1 , Arnold Bolomsky  1 , Simona Caltagirone  2 , Martin Schreder  1 , Sabine Pfeifer  1 , Heinz Gisslinger  3 , Niklas Zojer  1 , Ulrich Jäger  3 , Antonio Palumbo  2
Affiliations
Multicenter Study

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

Daniel Heintel et al. Br J Haematol. 2013 Jun.

Abstract

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 3·45 in patients who achieved complete response, and 3·75, 2·01, 0·78, and 0·70 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 = 0·48; P < 0·001). Among established prognostic parameters, only beta-2-microglobulin correlated with cereblon (r = 0·66; P < 0·001). A close association of CRBN with interferon regulatory factor 4 (IRF4) (P < 0·001) and with CTNNB1 (P < 0·001) 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.

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