Association between CYP3A4, CYP3A5, and ABCB1 Genotype, Tacrolimus Concentrations, and Outcomes Among Allogeneic Hematopoietic Stem Cell Transplantation Patients

Background Successful treatment with tacrolimus (TAC) to prevent graft versus host disease (GVHD) and minimize TAC-related toxicities among allogeneic hematopoietic stem cell transplantation (alloHSCT) recipients is contingent upon achieving and maintaining plasma trough concentrations within a narrow therapeutic range. Despite standardized weight-based dosing, inter-individual variability is observed in TAC trough concentrations which may in part be attributable to pharmacogenetic variants influencing the pharmacokinetic disposition of TAC. The primary objective was to investigate the association between CYP3A4, CYP3A5, or ABCB1 genotype and the proportion of patients that attained an initial TAC trough concentration in the therapeutic range following initiation of intravenous (IV) TAC and conversion to oral (PO) TAC administration. Additional associations with clinical outcomes were also explored.