Pharmacokinetics and Efficacy of Generic Melphalan Is Comparable to Innovator Formulation in Patients With Multiple Myeloma Undergoing Autologous Stem Cell Transplantation.

High-dose melphalan (MEL) is the standard conditioning regimen used for autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM). Generic MEL is routinely used in various transplant centers across the world including ours due to its reduced cost and ease of availability. We compared the pharmacokinetics (PK) and the clinical efficacy of generic MEL with that of the innovator formulation in MM patients undergoing ASCT. Sixty-three patients diagnosed with MM receiving high-dose MEL were included in this study. MEL levels in plasma were measured using a liquid chromatography tandem mass spectrometry (HPLC/MS-MS) protocol and non-linear mixed effects modeling was used to evaluate the PK of the data. The interindividual variability (IIV) in MEL area under the concentration versus time curve (AUC) and clearance (CL) were 4.39, 5.88-fold for generic, and 4.34, 6.85-fold for the innovator formulation, respectively. The median MEL AUC and CL were comparable between the 2 formulations. The population PK analysis showed age and creatinine CL as the only significant covariates explaining IIV in MEL AUC/CL. Analysis of MEL PK parameters with clinical outcome showed no significant differences in terms of onset and severity of mucositis, day to neutrophil and platelet engraftment, as well as response status on day 100 post ASCT between patients receiving generic or innovator formulations of MEL. In addition, neither MEL AUC nor CL was found to be associated with day +100 response. Our study suggests that the PK and efficacy of the generic MEL is comparable to the innovator formulation.