Pharmacokinetics of High-Dose Propylene Glycol Free Melphalan in Multiple Myeloma Patients Undergoing Autologous Hematopoietic Cell Transplantation.

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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 May 08;:

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

Abstract
High dose melphalan followed by autologous stem cell transplant (ASCT) is standard of care for eligible patients with multiple myeloma (MM). EVOMELAR (propylene glycol-free melphalan HCl, PG-Free Mel) was approved by the FDA as conditioning therapy for ASCT in MM in two daily 100 mg/m2 doses for a total dose of 200 mg/m2. In this phase II, open-label study; PG-Free Mel (EvomelaR) conditioning was given at single dose of 200 mg/m2 on day -2 pre-ASCT in order 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-minute post-infusion while there was considerable variation in the maximum plasma concentration (Cmax) and area under concentration time curve (AUC). Median Cmax was 7380 ng/ml with an interquartile range (IQR) 6522 to 8027 ng/ml. Similarly, median AUC was 53,3552 ng/ml*min (IQR 45,0850 to 66,2936 ng/ml*min). 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 (>VGPR) of 75%. In conclusion, while PG-Free Mel at a single dose of 200mg/m2 was safe, considerable PK variability was observed with highest quartile having ~ 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.

PMID: 29751116 [PubMed - as supplied by publisher]

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