Outcomes In Patients with Multiple Myeloma Following Autologous Stem Cell Transplantation Using Intravenous Busulfan and Melphalan: A Matched Comparison to a Double Autologous Transplant Strategy

We have previously reported a high response rate with a conditioning regimen consisting of intravenous busulfan (ivBu) and melphalan (Mel) in patients with multiple myeloma (MM) undergoing autologous stem cell transplant (ASCT) (Blanes M et al, Leuk Lymphoma 2009). In this case-matched study, we analyze the efficacy and toxicity of ivBuMel as conditioning regimen before ASCT in 51 patients with newly diagnosed MM. Their clinical outcome was compared with that of a control group of 102 pair mates included in the Spanish PETHEMA/GEM2000 study of tandem transplant (control group).

Patients in the control group were transplanted between 2002 and 2005, while patients in the ivBuMel group underwent ASCT between 2005 and 2009. Controls were matched with respect to sex, age, Durie-Salmon and ISS stage at diagnosis, and disease status at transplant. The conditioning regimen comprised iv Bu (3.2 mg/kg in a single daily dose, days -5 to -3) and Mel (140 mg/m², day -2). Patients in the control group underwent a first ASCT after Mel 200 mg/m² (Mel 200) in a single dose on day -2 followed in patients failing to achieve a complete response (CR) by a second autologous transplant. The conditioning regimen administered in the second transplant was either Mel 200 or a combination of cyclophosphamide, carmustine, and etoposide.

There were no differences in the hematopoietic recovery and mild or moderate mucositis was the toxicity most frequently observed in both groups of patients. Two (4%) patients died due to transplant-related complications in the ivBuMel group and 5 (5%) in the control group. The CR/near CR (nCR) rate was 51 % in both groups. After median follow-up of 32 and 40.5 months in the ivBuMel and control group, respectively, median progression free survival (PFS) was 37.6 for patients who received ivBuMel and 26.5 months for those in the control group. At 4 years, overall survival and PFS was 65±10% and 42±9% in the ivBuMel and 62±5% and 32± 5% in the control group, respectively (P = NS). For patients achieving CR/nCR after ASCT, the 4-years PFS rate was 52±14% and 40±8% in ivBuMel and control group, respectively (P = 0.3). Finally, in patients achieving partial response or less after transplant, the 4-years PFS rate was 33±12% and 23±6% in ivBuMel and tandem transplant group, respectively (P = 0.3).

Results of this case-matched study suggest that the use of ivBuMel conditioning regimen before ASCT in patients with newly diagnosed MM is associated with low transplant-related morbidity and mortality and a high anti myeloma efficacy that compares favourably with a tandem transplant strategy.

No relevant conflicts of interest to declare.