Open AccessPharmacokinetic‐Pharmacodynamic Model of Neutropenia in Patients With Myeloma Receiving High‐Dose Melphalan for Autologous Stem Cell Transplant
Author(s) -
Cho Yu Kyoung,
Irby Donald J.,
Li Junan,
Sborov Douglas W.,
Mould Diane R.,
Badawi Mohamed,
Dauki Anees,
Lamprecht Misty,
Rosko Ashley E.,
Fernandez Soledad,
Hade Erinn M.,
Hofmeister Craig C.,
Poi Ming,
Phelps Mitch A.
Publication year - 2018
Publication title -
cpt: pharmacometrics and systems pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 37
ISSN - 2163-8306
DOI - 10.1002/psp4.12345
Subject(s) - melphalan , medicine , multiple myeloma , neutropenia , pharmacodynamics , autologous stem cell transplantation , pharmacokinetics , granulocyte colony stimulating factor , oncology , regimen , pharmacology , transplantation , absolute neutrophil count , population , chemotherapy , environmental health
High‐dose melphalan (HDM) is part of the conditioning regimen in patients with multiple myeloma ( MM ) receiving autologous stem cell transplantation ( ASCT ). However, individual sensitivity to melphalan varies, and many patients experience severe toxicities. Prolonged severe neutropenia is one of the most severe toxicities and contributes to potentially life‐threatening infections and failure of ASCT . Granulocyte‐colony stimulating factor (G‐ CSF ) is given to stimulate neutrophil proliferation after melphalan administration. The aim of this study was to develop a population pharmacokinetic/pharmacodynamic ( PK / PD ) model capable of predicting neutrophil kinetics in individual patients with MM undergoing ASCT with high‐dose melphalan and G‐ CSF administration. The extended PK / PD model incorporated several covariates, including G‐ CSF regimen, stem cell dose, hematocrit, sex, creatinine clearance, p53 fold change, and race. The resulting model explained portions of interindividual variability in melphalan exposure, therapeutic effect, and feedback regulation of G‐ CSF on neutrophils, thus enabling simulation of various doses and prediction of neutropenia duration.