Patients exposed to, and putatively resistant to, lenalidomide had lower CRBN levels in paired samples before and after therapy. In summary, CRBN is an essential requirement for IMiD activity and a possible biomarker for the clinical assessment of antimyeloma efficacy....CRBN is required for lenalidomide and pomalidomide response, we further investigated the CRBN expression level in 9 MM patients with physician-reported lenalidomide resistance. In 8 of 9 MM patients, with pre- and post-lenalidomide therapy samples analyzed by quantitative PCR, the CRBN expression level showed a significant reduction (20%-90% reduction) at the time of drug resistance (Figure 5A).