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

Autor:	Junan, Li, Yu Kyoung, Cho, Douglas W, Sborov, Mitch A, Phelps, Craig C, Hofmeister, Ming J, Poi
Rok vydání:	2022
Předmět:	Cancer Research Genotype Tandem Mass Spectrometry Genetics Humans Cytochrome P-450 CYP3A Multiple Myeloma Melphalan Molecular Biology Biochemistry Chromatography Liquid Stem Cell Transplantation Research Article
Zdroj:	Cancer Genomics Proteomics
ISSN:	1790-6245 1109-6535
DOI:	10.21873/cgp.20360
Popis:	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 CYP3A4*1B (rs2940574) and CYP3A5*3 (rs776746) variations on pharmacokinetic properties of melphalan and clinical outcomes in multiple myeloma (MM) patients. Patients and Methods: Genotypes of CYP3A4*1B (rs2940574) and CYP3A5*3 (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/ΜS). Results: CYP3A4*1B/*1B and CYP3A5*3/*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 CYP3A5*3/*3 variations might influence melphalan therapy in MM patients through yet-to-be-identified mechanisms.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7037d122c1600e04ad1b47ffbaf15e15 https://doi.org/10.21873/cgp.20360 Zobrazit plný text záznamu