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Pharmacokinetics of High-Dose Propylene Glycol-Free Melphalan in Multiple Myeloma Patients Undergoing Autologous Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant 2018 Aug;24(8):1610-1614 PMID: 29751116

Pubmed ID

29751116

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 doses for a total dose of 200 mg/m. In this phase II, open-label study PG-Free Mel (Evomela) conditioning was given at single dose of 200 mg/m 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) and area under concentration time curve (AUC). Median C 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 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.

Author List

Dhakal B, D'Souza A, Lakshman A, Hamadani M, Chhabra S, Thompson R, Shah N, Pasquini M, Hari P

Authors

Saurabh Chhabra MD Assistant Professor in the Medicine department at Medical College of Wisconsin
Anita D'Souza MD Assistant Professor in the Medicine department at Medical College of Wisconsin
Binod Dhakal MD Assistant Professor in the Medicine department at Medical College of Wisconsin
Mehdi H. Hamadani MD Professor in the Medicine department at Medical College of Wisconsin
Parameswaran Hari MD Chief, Professor in the Medicine department at Medical College of Wisconsin
Marcelo C. Pasquini MD, MS Associate Professor in the Medicine department at Medical College of Wisconsin




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