The Food and Drug Administration has approved a new propylene glycol–free formulation of melphalan hydrochloride as a high-dose conditioning treatment for autologous stem cell transplantation, and as a palliative therapy for multiple myeloma.
Evomela (Spectrum Pharmaceuticals) is intended to be reconstituted with normal saline at the time of intravenous administration. The solution is stable for 4 hours using Captisol, a proprietary agent containing modified cyclodextrin. It is also stable for 1 hour after reconstitution.
Extended stability without the need for propylene glycol is its major advantage over the other formulations of melphalan, a chemotherapy agent originally approved in 1964, according to a statement by Spectrum.
Evomela was approved on the basis of a phase IIa pharmacokinetic trial comprising 24 patients undergoing autologous stem cell transplantation. Evomela was bioequivalent with Alkeran, with a 10% higher maximum plasma concentration and area under the plasma concentration-time curve ( Bone Marrow Transplant. 2014 Aug;49:1042-5 ).
According to that, and other studies, adverse reactions included decreased neutrophil count (100%), decreased white blood cell count (100%), decreased lymphocyte count (98%), decreased platelet count (98%), diarrhea (93%), nausea (90%), fatigue (77%), hypokalemia (74%), anemia (66%), and vomiting (64%). About 2% of patients have experienced hypersensitivity reactions.
For palliative treatment, the recommended does is 16 mg/m2 infused over 15-20 minutes at 2-week intervals for four doses, and then, after adequate recovery from toxicity, at 4-week intervals.
For conditioning treatment, the recommended does is 100 mg/m2 per day infused over 30 minutes for 2 consecutive days before stem cell transplant.