Propylene glycol (PG)-free melphalan versus PG-melphalan as conditioning for autologous hematopoietic cell transplantation for myeloma

High-dose melphalan (Mel) conditioning before autologous hematopoietic cell transplantation (autoHCT) is standard-of-care for transplant eligible multiple myeloma. The traditional lyophilized Mel formulation has inadequate solubility and stability after reconstitution leading to the use of propylene glycol (PG) as solubilizing agent. A newer PG-free Mel preparation (Evomela®), uses the beta cyclodextrin captisol as a solubilizing agent and was approved by the US FDA as a conditioning agent based on a single phase IIb study showing bioequivalence. We compared the outcomes of consecutive myeloma patients receiving autoHCT using the two formulations of Mel for conditioning as our center switched from using the older formulation (PG-Mel) for the newer one (PGF-Mel). Of 294 autoHCT patients, 162 received PG-Mel, and 132 received PGF-Mel conditioning. PGF-Mel patients were older and had lower KPS. PGF-Mel was associated with faster neutrophil recovery (median, 12 vs. 13 days, p<0.001), fewer grade 3-4 infections within 30 days of autoHCT (1.5 vs. 8.0%, p=0.048), and decreased 30-day rehospitalization rates (6.8 vs. 17.9%, p=0.04), which were confirmed by propensity weighted analysis. No significant differences were detected in mucositis, organ toxicity, myeloma responses or 100-day mortality.