Associations of High‐Dose Melphalan Pharmacokinetics and Outcomes in the Setting of a Randomized Cryotherapy Trial

作者：YK Cho, DW Sborov, Monika Lamprecht, J. Li, J Wang, Erinn M. Hade, Yue Gao, Karen Tackett, Nicole Williams, DM Benson, YA Efebera, AE Rosko, SM Devine, Ming Poi, CC Hofmeister, Mitch A. Phelps · 发表于：Clinical Pharmacology & Therapeutics · 年份：2017 · DOI：10.1002/cpt.644 · 被引用次数：38 · 研究领域：Multiple Myeloma Research and Treatments、Hematopoietic Stem Cell Transplantation、Silymarin and Mushroom Poisoning

High-dose melphalan followed by autologous stem cell transplantation remains the standard of care for eligible patients with multiple myeloma, but disease response and toxicity, including severe mucositis, varies among patients. Our randomized trial investigated duration of cryotherapy (2 and 6 h) for reduction of mucositis prevalence and severity and explored factors associated with variability in pharmacokinetics and outcomes from melphalan therapy. The results demonstrate that 2-h is at least as effective as 6-h cryotherapy in decreasing severe mucositis. From a population pharmacokinetic model, we identified that fat-free mass, hematocrit, and creatinine clearance were significant covariates, as reported previously. Furthermore, we observed the rs4240803 SLC7A5 polymorphism was significantly associated with pharmacokinetic variability, and pharmacokinetics was associated with both mucositis and neutropenia. However, melphalan exposure was not associated with progression-free or overall survival in our dataset. These findings contribute to ongoing efforts to personalize melphalan dosing in transplant patients.