Binod Dhakal, Anita D'Souza, Arjun Lakshman, Mehdi Hamadani, Saurabh Chhabra, Robert Thompson, Nirav Shah, Marcelo Pasquini, Paramweswaran Hari

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.