Polymorphisms in the promoter region of the CRBN gene as a predictive factor for the first-line CTD therapy in multiple myeloma patients

Cereblon is a primary molecular target for immunomodulatory drugs. The aim of this study was to evaluate the influence of selected clinical and molecular factors including single nucleotide polymorphisms (SNPs) in CRBN gene on the efficacy of first line CTD (cyclophosphamide, thalidomide, dexamethasone) chemotherapy in patients with multiple myeloma. Study group consisted of 68 patients. Analysis of CRBN gene SNPs (rs6768972, rs1672753) was performed using Real-Time PCR genotyping technique. Median progression free survival (PFS) was 15 months and overall survival (OS) 79 months. Factors associated with significantly shorter OS included ISS 3, kidney disease, weight loss, anemia, thrombocytopenia, hypoalbuminemia, elevated β2-microglobuline and CRP. The presence of t(4;14) was associated with significantly shorter PFS and OS. Both examined SNPs proved to be statistically significant, independent predictive factors of efficacy of the CTD chemotherapy. The presence of AA genotype (rs6768972) correlated with longer median PFS (18 vs 9 months; HR=0.49,95% CI: 0.26-0.91, p=0.0062). Conversely, in the carriers of CC genotype (rs1672753) significantly shorter median PFS was observed (4 vs 16 months; HR=3.93, 95% CI: 0.26-59.64, p=0.0321). In conclusion, SNPs of the CRBN gene may be useful in qualifying patients for treatment with regimens containing thalidomide.