G-CSF Plus Decitabine and Busulfan-Cyclophosphamide Conditioning for Patients With MDS-RAEB and Secondary AML Evolving From MDS

Results from a Randomized Phase 3 Trial

Combining granulocyte-colony stimulating factor (G-CSF) plus decitabine and busulfan-cyclophosphamide conditioning regimen reduced the 2-year cumulative incidence of relapse among patients with myelodysplastic syndrome (MDS)-refractory anemia with excess blasts (RAEB), as well as patients with secondary acute myeloid leukemia (AML) evolving from MDS undergoing allogeneic hematopoietic stem-cell transplantation (alloHSCT), according to a phase 3 trial published in The Lancet Haematology. 

According to Li Xuan, MD, Southern Medical University, Guangzhou, China, and coauthors, “Relapse remains high in patients with myelodysplastic syndrome-refractory [anemia] with excess blasts or secondary acute myeloid [leukemia] evolving from myelodysplastic syndrome undergoing allogeneic [hematopoietic] stem-cell transplantation.” 

In an attempt to reduce the high rate of relapse, Dr Xuan et al aimed to assess whether adding G-CSF and decitabine to the busulfan-cyclophosphamide conditioning regimen would be more effective. The primary endpoint of this multicenter phase 3 trial was the cumulative incidence of relapse at 2 years, and the secondary endpoints were safety and tolerability. 

202 eligible patients with MDS-refractory anemia with excess blasts (MDS-RAEB), or secondary AML evolving from MDS, and HSCT comorbidity index ranging from 0 to 2, were enrolled in this study. Patients were randomized 1 to 1 and were administered either G-CSF plus decitabine and busulfan-cyclophosphamide conditioning (n=101), or just busulfan-cyclophosphamide conditioning (n=101). 

At a median follow-up of 32.4 months, the 2-year cumulative incidence of relapse was 10.9% for patients who received G-CSF plus decitabine and busulfan-cyclophosphamide conditioning versus 24.8% for patients who received just busulfan-cyclophosphamide conditioning. 

In terms of safety, the most common grade 3 to 4 adverse events within 100 days of treatment in the G-CSF plus decitabine and busulfan-cyclophosphamide conditioning arm versus busulfan-cyclophosphamide conditioning arm were infections (34% vs 32%), acute graft-versus-host disease (30% vs 30%), and gastrointestinal toxicity (28% vs 29%). In the G-CSF plus decitabine and busulfan-cyclophosphamide conditioning arm, 11 patients did not survive due to adverse events, compared to 13 in the busulfan–cyclophosphamide arm, all unrelated to treatment. 

In conclusion, study authors stated, “Our results suggest that G-CSF, decitabine, and busulfan–cyclophosphamide conditioning is a better choice than busulfan–cyclophosphamide conditioning for patients with myelodysplastic syndrome-RAEB or secondary acute myeloid leukemia evolving from myelodysplastic syndrome undergoing allogeneic HSCT. This conditioning could be a suitable therapuetic option for this patient population."

Source:  

Xuan L, Dai M, Jiang E, et al. The effect of granulocyte-colony stimulating factor, decitabine, and busulfan–cyclophosphamide versus busulfan–cyclophosphamide conditioning on relapse in patients with myelodysplastic syndrome or secondary acute myeloid leukaemia evolving from myelodysplastic syndrome undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised, phase 3 trial. Published 2023 January 23. Lancet Haematol. 10(3):e178-e190. doi:10.1016/S2352-3026(22)00375-1