The lyophilized formulation of
melphalan has several limitations based on its marginal solubility, limited stability after reconstitution, and the requirement to reconstitute it in
propylene glycol (PG). PG-free
melphalan (Evomela; Spectrum
Pharmaceuticals, Irvine CA) overcomes these limitations by using the solubilizing agent
Captisol (
Ligand Pharmaceuticals, Inc., LaJolla CA) to improve the stability of the reconstituted
melphalan and avoid the potential toxicities of PG. This phase II study investigated the safety and efficacy of high-dose PG-free
melphalan when included in the
carmustine,
etoposide, and
cytarabine (
BEAM) regimen for adult patients with
non-Hodgkin lymphoma (NHL) or
Hodgkin lymphoma (HL).
Carmustine,
etoposide, and
cytarabine were given at standard doses on day -6 through day -3. PG-free
melphalan, 140 mg/m2, was infused over 30 minutes on day -2. The primary endpoint was toxicity. Fifty patients (33 NHL/17 HL) completed BEAM with PG-free
melphalan and stem cell infusion. The most common grades 3 to 4 nonhematologic toxicities were neutropenic
fever (68%),
infections (36%), and
electrolyte abnormalities. Forty-one patients (82%) had
oral mucositis, which was mostly grades 1 to 2 (6% grade 3). Moderate or severe gastrointestinal toxicities were uncommon. There were no treatment-related deaths. Forty-nine patients (98%) had neutrophil and platelet engraftment at a median of 10 and 19 days, respectively. At response assessment at 60 to 100 days after autologous
stem cell transplantation, 42 patients (82%) were
in complete remission, 2 in partial remission, and 6 had progressive disease. Progression-free survival at 1 year was 70%. These results demonstrate that PG-free
melphalan can be used in place of the standard, lyophilized formulation of
melphalan in the
BEAM regimen for
lymphoma patients undergoing autologous
stem cell transplantation. It has a safety profile that compares favorably with standard lyophilized
melphalan, and the engraftment rate and response rates were consistent with expectations.