Comparison of busulfan + melphalan to melphalan 200 mg/m2 as preparative regimen for autologous transplantation in multiple myeloma

Background: High-dose chemotherapy with melphalan 200 mg/m2 (Mel 200) followed by autologous hematopoietic stem cell transplantation (auto-HCT) is the standard treatment for transplant-eligible patients (pts) with multiple myeloma (MM). Most patients eventually relapse after auto-HCT and in efforts to improve the efficacy of the preparative regimen, several groups have evaluated the combination of busulfan (Bu) and melphalan (Mel). We studied the safety and efficacy of a combination of Bu and Mel (Bu-Mel) in patients with advanced lymphoid malignancies, including MM. (Kebriaei P, et al., Biol Blood Marrow Transplant 2011; 17: 412-420). In this study we compared outcomes of patients with MM who received Bu-Mel with a control group of patients who received Mel 200 for auto- HCT for MM. Methods: We identified 30 patients with MM in first remission who received Bu-Mel followed by auto-HCT between 1/2005 and 10/2010. They were compared to a control group (4:1) of 120 patients with MM who received Mel 200 as conditioning regimen for auto-HCT. The groups were matched for year of auto- HCT, age at auto-HCT (+/- 4 yrs), cytogenetic abnormalities, and disease status at auto-HCT. The primary objective was to study impact of conditioning regimens on complete (CR) and overall response rate (ORR), progression-free (PFS) and overall survival (OS). Results: Patient characteristics and major outcomes are summarized in the attached Table. Bu-Mel and Mel 200 groups were similar in median age, renal function and chemosensitivity at auto- HCT, and time from diagnosis to auto-HCT (Table). Median time to neutrophil engraftment in both groups was 10 days (p = 0.8). There was no significant difference in 100-day transplantrelated mortality (0% vs. 0.8%, p = 0.2) or grade 2-4 non-hematologic toxicity between Bu-Mel and Mel 200 (80% vs. 66%, p = 0.18) or veno-occlusive disease (none in either group). CR rates in Bu-Mel and Mel 200 were 30% vs. 34% (p = 0.82, Table). Median follow up was 27.3 months. Median PFS for Bu-Mel and Mel 200 were 24.1 and 26.2 months, respectively (p = 0.43, Figure 1). Median OS for Bu-Mel and Mel 200 has not yet been reached (p = 0.24, Figure 2). Conclusions: In this large single center study with long follow up, we demonstrated that a preparative regimen of Bu-Mel is comparable to Mel 200 in safety and efficacy. The two regimens will be compared in a prospective, randomized trial. (Table presented).