Polymorphisms in the promoter region of the CRBN gene as a predictive factor for the first-line CTD therapy in multiple myeloma patients
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Aneta Szudy-Szczyrek1, Radosław Mlak2, Michał Szczyrek3,4, Sylwia Chocholska1, Jacek Sompor5, Adam Nogalski5, Teresa Małecka-Massalska2 and Marek Hus1
1Department of Haematooncology and Bone Marrow Transplantation, Medical University of Lublin, 20-081 Lublin, Poland
2Department of Human Physiology, Medical University of Lublin, 20-080 Lublin, Poland
3Department of Internal Medicine in Nursing, Medical University of Lublin, 20-090 Lublin, Poland
4Department of Pneumology, Oncology and Allergology, Medical University of Lublin, 20-950 Lublin, Poland
5Department of Trauma Surgery and Emergency Medicine, Medical University of Lublin, 20-081 Lublin, Poland
Aneta Szudy-Szczyrek, email: [email protected]
Keywords: multiple myeloma; thalidomide; cereblon; polymorphism
Received: February 21, 2018 Accepted: April 16, 2018 Published: May 08, 2018
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.
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