Journal article
Pharmacokinetics of High-Dose Propylene Glycol-Free Melphalan in Multiple Myeloma Patients Undergoing Autologous Hematopoietic Cell Transplantation
Biology of blood and marrow transplantation, Vol.24(8), pp.1610-1614
01 Aug 2018
PMID: 29751116
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
High-dose melphalan followed by autologous stem cell transplant (ASCT) is standard of care for eligible patients with multiple myeloma (MM). Evomela (propylene glycol-free melphalan HCl [PG-Free Mel]; Spectrum Pharmaceuticals, Irvine, CA) was approved by the US Food and Drug Administration as conditioning therapy for ASCT in MM in 2 daily 100-mg/m(2) doses for a total dose of 200 mg/m(2). In this phase II, open-label study PG-Free Mel (Evomela) conditioning was given at single dose of 200 mg/m(2) on day -2 pre-ASCT to establish pharmacokinetic (PK) parameters and safety. Twenty-four patients (median age, 64 years) were enrolled between August 2016 and February 2017. Myeloablation followed by successful neutrophil engraftment occurred at a median of 10 days in all patients. Peak melphalan concentration was observed at 10 minutes after infusion, whereas there was considerable variation in the maximum plasma concentration (C-max) and area under concentration time curve (AUC). Median C-max was 7380 ng/mL (interquartile range [IQR], 6522 to 8027). Similarly, median AUC was 533,552 ng/mL.min (IQR, 450,850 to 662,936). PG-Free Mel had an acceptable safety profile regardless of the exposure, with no mortality and an overall response rate of 96% and a very good partial response rate of 75%. In conclusion, although PG-Free Mel at a single dose of 200 mg/m(2) was safe, considerable PK variability was observed with the highest quartile having an -3-fold higher AUC than the first quartile, suggesting that strategies for higher targeted exposure could be explored in future trials to optimize clinical benefit. (C) 2018 American Society for Blood and Marrow Transplantation.
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Details
- Title
- Pharmacokinetics of High-Dose Propylene Glycol-Free Melphalan in Multiple Myeloma Patients Undergoing Autologous Hematopoietic Cell Transplantation
- Creators
- Binod Dhakal - Medical College of WisconsinAnita D'Souza - College Station Medical CenterArjun Lakshman - Mayo ClinicMehdi Hamadani - Medical College of WisconsinSaurabh Chhabra - Medical College of WisconsinRobert Thompson - Medical College of WisconsinNirav Shah - Medical College of WisconsinMarcelo Pasquini - Medical College of WisconsinParamweswaran Hari - College Station Medical Center
- Publication Details
- Biology of blood and marrow transplantation, Vol.24(8), pp.1610-1614
- Publisher
- Elsevier
- Number of pages
- 5
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- General Internal Medicine
- Web of Science ID
- WOS:000443668100012
- Scopus ID
- 2-s2.0-85048069667
- Other Identifier
- 991022059919104721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Hematology
- Immunology
- Transplantation