评估 CYP3A4*1B 和 CYP3A5*3 变异对自体造血干细胞移植多发性骨髓瘤患者药代动力学行为和临床结局的影响。
Evaluating the Impacts of CYP3A4*1B and CYP3A5*3 Variations on Pharmacokinetic Behavior and Clinical Outcomes in Multiple Myeloma Patients With Autologous Stem Cell Transplant.
机构信息
Division of Pharmacy Practice and Science, College of Pharmacy, The Ohio State University, Columbus, OH, U.S.A.;
Comprehensive Cancer Center, The Ohio State University, Columbus, OH, U.S.A.
出版信息
Cancer Genomics Proteomics. 2023 Jan-Feb;20(1):9-17. doi: 10.21873/cgp.20360.
BACKGROUND/AIM: There exists considerably large interpatient variability in pharmacokinetic exposure of high dose melphalan in multiple myeloma patients with hematopoietic stem-cell transplantation. In this study, we aimed to evaluate the potential impacts of CYP3A41B (rs2940574) and CYP3A53 (rs776746) variations on pharmacokinetic properties of melphalan and clinical outcomes in multiple myeloma (MM) patients.
PATIENTS AND METHODS
Genotypes of CYP3A41B (rs2940574) and CYP3A53 (rs776746) were determined by validated gene-specific real-time PCR (RT-PCR) assays using DNA samples from 108 MM patients; plasma concentrations of melphalan at different time points were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
RESULTS
CYP3A4*1B/1B and CYP3A53/*3 carriers appeared to have a short median progression-free survival time and a higher maximum melphalan plasma concentration than non-carriers [792 vs. over 950 days, p=0.08; 9.91 (2.67, 34.03) vs. 8.66 (4.46, 17.61) mg/l, p=0.039].
CONCLUSION
CYP3A4*1B/1B and CYP3A53/*3 variations might influence melphalan therapy in MM patients through yet-to-be-identified mechanisms.
背景/目的：在接受造血干细胞移植的多发性骨髓瘤患者中，大剂量美法仑的药代动力学暴露存在相当大的个体间变异性。本研究旨在评估 CYP3A41B(rs2940574) 和 CYP3A53(rs776746) 变异对多发性骨髓瘤(MM)患者美法仑药代动力学特性和临床结局的潜在影响。
方法
采用经验证的基因特异性实时 PCR(RT-PCR)测定法，使用来自 108 例 MM 患者的 DNA 样本，确定 CYP3A41B(rs2940574) 和 CYP3A53(rs776746) 的基因型；采用液相色谱-串联质谱(LC-MS/MS)定量测定不同时间点美法仑的血浆浓度。
结果
CYP3A4*1B/1B 和 CYP3A53/*3 携带者的中位无进展生存期似乎较短，最大美法仑血浆浓度较高[792 天与超过 950 天，p=0.08；9.91(2.67,34.03)mg/L 与 8.66(4.46,17.61)mg/L，p=0.039]。
结论
CYP3A4*1B/1B 和 CYP3A53/*3 变异可能通过尚未确定的机制影响 MM 患者的美法仑治疗。
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