Poster Session I: Myeloma and other monoclonal gammopathies - Clinical
Cereblon (CRBN) was identified as target protein of Immunomodulatory Drugs (ImiDs). It was shown that its decreased expression was related to ImiDs resistance and carcinogenesis. However, very little is known about the importance of serum CRBN concentrations.
To determine serum CRBN in MM patients treated with RD (lenalidomide-dexamethasone) and to study eventual correlations with disease characteristics.
We studied 91 MM patients from RD initiation until last follow up or death; their files were reviewed after patients' informed consent was obtained, while clinical and laboratory characteristics were collected. Frozen patients' sera, drawn at the time of RD treatment (68 patients), best response (59 patients) and at relapse/refractoriness to Rd (54 patients) were retrospectively analyzed. CRBN was measured by commercially available ELISA kit (cloud clone), according to the manufacturer's instructions. Twenty healthy individuals (HI) were also tested. Statistical analysis was performed using the SPSS v24.0. software.
The median age of patients was 70 years (56% men, 44% women). Ig type was IgG in 64%, IgA in 22%, light-chain in 11% and IgD or biclonal in 3%. Thirty percent of patients were staged ISS 1, 20% ISS 2 and 51% ISS 3. RD was administered in 1st line in 8% of patients, second in 37%, third in 26%, forth in 16% and in 5th to 9th line in 13%. Median serum CRBN levels at RD initiation were 247 pg/ml (0-9760), 148,8 pg/ml (0 -9940) at best response and 294 pg/ml (0-9840) at relapse/resistance to RD. In HI CRBN ranged from 0 to 580 pg/ml. CRBN values at RD initiation were negatively correlated with paraprotein levels (τ = −0,204, p = 0,05). At best response they marginally correlated with quality of response (τ = −0,250, p = 0,055). Median serum CRBN level was used as a cut-off point in survival analysis. Median overall survival was 70 months (range, 7-345) and time until next treatment was 14 months (range, 1-110). Five-year survival was improved in patients with CRBN levels below median at the time of RD initiation (p = 0,03), during best response (p = 0,035), and in relapse/refractory patients to Rd (p = 0,05) while time to next treatment was significantly shorter in patients with CRBN levels above median at best response (p = 0,026).
serum CRBN levels below median were related to a better 5-year survival post RD and to time to next treatment. Mechanisms leading to protein release in the serum possibly explain this apparent discrepancy with the reported impact of low CRBN expression.