Blanes and collegues conducted a prospective, multicenter study that included 153 patients and compared the outcomes in patients with MM receiving 2 different conditioning regimens: intravenous busulfan (BU) 9.6 mg/kg and MEL 140 mg/m2 (BUMEL140) versus MEL200 alone. No differences in progression-free survival (PFS), overall response (OR), or complete response (CR) were found.  Both groups also had similar toxicity profiles. The median follow-up of both groups was somewhat limited at 63 months (MEL200) and 50 months (BUMEL140). 

The authors of this study recently published a letter to the editor in which they updated some of their results of the original 2013 paper.6 They collected additional follow-up data in the BUMEL140 group, which extended the median follow-up to 56 months (compared with 50 months in the 2013 study) which led to a median PFS of 33 months in the BUMEL140 group compared to 24 months in the MEL200 group (P =.04). This difference was not statistically significant in the initial 2013 analysis. 

Interestingly, the median OS did not differ between the groups at 65.7 months in the BUMEL140 group compared with 65.1 months in the MEL200 group. The authors did highlight that 10 patients in the BUMEL140 group sustained their response for more than 9 years after transplantation without any serious long-term adverse events experienced. 

As seen with this update, there does appear to be accumulating evidence to support routinely using BUMEL as a conditioning regimen. In this same letter to the editor, the authors cited a recent study conducted by Jung and colleagues, in which BUMEL was used in 99 patients with MM and showed an OR of 94%, CR of 43.5%, median follow-up of 26.1 months, and median PFS of 27.2 months, which is similar to their updated data that was presented. 

It appears that collecting longer-term data in patients with MM who are undergoing conditioning regimens is crucial to understanding their clinical outcomes and safety profiles. Optimizing conditioning regimens leading up to ASCT could help prevent relapse and limit adverse events in the future. 

References

  1. Gay F, Oliva S, Petrucci MT, et al. Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: a randomized, multicentre, phase 3 trial. Lancet Oncol. 2015;16(16):1617-1629.
  2. Palumbo A, Cavallo F, Gay F, et al. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med. 2014;371(10):895-905.
  3. Sonneveld P et al. Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group. Blood. 2016;127(24):2955-2962.
  4. Gyurkocza B, Sandmaier BM. Conditioning regimens for hematopoietic cell transplantation: one size does not fit all. Blood. 2014;124(3):344-353.
  5. Blanes M et al. Intravenous busulfan and melphalan as a conditioning regimen for autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: a matched comparison to a melphalan-only approach. Biol Blood Marrow Transplant. 2013;19(1):69-74.
  6. Blanes M, Lorenzo JI, Ribas P, et al. Intravenous busulfan plus melphalan versus melphalan alone as conditioning regimen for patients with multiple myeloma [published online March 16, 2019]. Ann Hematol. doi: 10.1007/s00277-019-03663-5
  7. Jung SH, Lee JJ, Kim JS, et al; Korean Multiple Myeloma Working Party. Phase 2 study of an intravenous busulfan and melphalan conditioning regimen for autologous stem cell transplantation in patients with multiple myeloma (KMM150). Biol Blood Marrow Transplant. 2018;24(5):923-929.