Serum Cereblon (CRBN) Levels Predict Long Term Post- Lenalidomide-Dexamethasone Survival in Multiple Myeloma (MM)...

Serum cereblon (CRBN) has been proposed as a target protein for immunomodulatory drugs (IMiDs). IMiDs are one of the backbone treatment options in multiple myeloma (MM), rendering CRBN an intriguing candidate for use as a biomarker in clinical settings. Ninety-two (92) MM patients, mostly relapsed/refractory and a few at diagnosis, were included in the study, from lenalidomide-dexamethasone (LD) initiation until last follow-up or death. Median CRBN at LD initiation (N = 68) treatment was 247 pg/mL (range, 0-9760 pg/mL), at the time of best response (BR) status (N = 59) 142.5 pg/mL (range, 0-9940 pg/mL) and in patients with relapse/refractory MM to LD regimen (N = 54) 298 pg/mL (range, 0-9840 pg/mL). CRBN in healthy individuals was almost undetectable and significantly lower compared to the CRBN at LD initiation (p = 0.003), at BR to LD (p = 0.012) and at relapse to LD (p = 0.002). CRBN was significantly lower at BR in contrast to LD initiation and relapse to LD (p = 0.04, p = 0.028). High levels of CRBN at treatment initiation correlated with early relapse to LD (≤12 months) (p = 0.03). Seven-year survival was improved in patients with CRBN levels below median measured at the time of LD initiation (p = 0.013) as well as at BR (p = 0.032). CRBN was associated with treatment response and is predictive of survival after LD.