Haematology Resident National and Kapodistrian University of Athens, Greece
Introduction: ImiDs resistance has been linked to Cereblon (CRBN), a crucial protein in Immunomodulatory Drugs' (ImiDs') activity. Our most recent research has demonstrated the possible predictive value of serum CRBN in MM patients. 1 Thus, the purpose of the presented study was to revise our findings from earlier research on the predictive significance of serum CRBN levels in MM patients treated with RD (lenalidomide-dexamethasone) and to study any correlations with disease activity thereafter.
Methods: We studied 92 MM patients from RD initiation until last follow up or death; Medical records were reviewed after patients' informed consent was obtained, while clinical and laboratory characteristics were collected. 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%. CRBN serum measurements at the time of RD treatment (69 patients), best response (59 patients) and at relapse/refractoriness to Rd (54 patients) were analyzed. CRBN was measured by commercially available ELISA kit (cloud clone), according to the manufacturer's instructions. Subsequent treatment lines after lenalidomide as well as patients' best responses to them, were recorded. Median serum CRBN level at each time point (RD initiation, at best response and Relapse) was used as a cut-off point in survival analysis . Statistical analysis was performed using the SPSS v28.0. software.
Results: Median levels of CRBN were 247 pg/ml (range, 0-9760) at RD initiation, at best response to RD 142.5 pg/ml (range, 0 -9944) and at Relapse 298 pg/ml (range, 0-9840). A statistically significant decrease on CRBN serum levels was observed at best response compared to RD initiation. (p=0.001). Seven-year survival was improved in patients with CRBN levels below median at the time of RD initiation (p=0,013), during best response (p=0,032) but not in relapse/refractory patients to Rd (p=0,357) and time to next treatment (p=0.121). Regarding the disease characteristics, CRBN serum levels correlated with increased bone marrow infiltration (≥60%). (p=0.05). Furthermore, high CRBN serum levels at RD initiation correlated with patients experiencing an early relapse(≤ 12 months) . Although intriguing, these patients responded to RD (≥PR) rather well. (p=0.03).
Conclusions: Our analysis on CRBN serum levels, revealed an extended 7-year survival of our patients with serum CRBN levels below median both at RD initiation and at best response. Early resistance to RD was correlated with CRBN serum levels in our patients and further study would be beneficial.
