Results from a phase 3 open label trial (ClinicalTrials.gov Identifier: NCT01413178) published in The Lancet Haematology suggest that busulfan plus melphalan may result in longer progression-free survival (PFS) compared with melphalan alone in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation (HSCT).
Patients with newly diagnosed multiple myeloma were accepted into the study between October 12, 2011, and March 22, 2017. Patients who were eligible for cell transplantation and met study inclusion criteria were randomly assigned in a 1-to-1 ratio to treatment with busulfan plus melphalan conditioning or melphalan conditioning alone. Patients in the busulfan plus melphalan group initially received a test dose of 32 mg/m² busulfan that was then pharmacokinetically adjusted to achieve a target daily area under the curve of 5000 mmol/minute, as well as 70 mg/m² melphalan daily for 2 days. Patients in the melphalan only group received a single dose of 200 mg/m² melphalan 2 days prior to autologous HSCT. The primary outcome of interest was PFS.
In total, 202 patients who received treatment were assessed for PFS: 104 patients in the busulfan plus melphalan group and 98 patients in the melphalan alone group. Median follow-up duration was 22.6 months (interquartile range [IQR], 15.2-47.1) in the busulfan plus melphalan group and 20.2 months (IQR, 8.8-46.6) in the melphalan alone group. Median PFS was 64.7 months (95% CI, 32.9-64.7) for the busulfan plus melphalan group compared with 43.5 months (95% CI, 19.9-not estimated) for the melphalan alone group (hazard ratio, 0.53; 95% CI, 0.30-0.91; P =.022).
Grade 2 or 3 mucositis occurred in 74% of patients (77/104) in the busulfan plus melphalan group compared with only 14% of patients (14/98) in the melphalan alone group.
The authors concluded that busulfan plus melphalan appeared to demonstrate superior progression-free survival compared with melphalan alone; however, they acknowledged the study limitations and called for their results to be verified in larger, randomized studies.
1. Bashir Q, Thall PF, Milton DR, et al. Conditioning with busulfan plus melphalan versus melphalan alone before autologous haemopoietic cell transplantation for multiple myeloma: an open-label, randomised, phase 3 trial [published online March 22, 2019]. Lancet Haematol. doi:10.1016/S2352-3026(19)30023-7