The following is a summary of “Busulfan Plus Fludarabine Compared With Busulfan Plus Cyclophosphamide for AML Undergoing HLA-Haploidentical Hematopoietic Cell Transplantation: A Multicenter Randomized Phase III Trial,” published in the October 2023 issue of Oncology by Ling, et al.
For a study, researchers sought to compare the outcomes of two conditioning regimens, busulfan plus fludarabine (BuFlu) and busulfan plus cyclophosphamide (BuCy), in HLA-haploidentical hematopoietic cell transplantation (haplo-HCT) for patients with acute myeloid leukemia (AML).
The open-label, randomized phase III trial was conducted at 12 hospitals in China. Patients aged 18-65 with AML were randomly assigned in a 1:1 ratio to receive either the BuFlu regimen (busulfan 0.8 mg/kg four times daily on days –6 to –3; fludarabine 30 mg/m2 once daily on days –7 to –3) or the BuCy regimen (same dose of busulfan; cyclophosphamide 60 mg/kg once daily on days –3 and –2). The primary endpoint was 1-year transplant-related mortality (TRM) in the intention-to-treat population and safety in the per-protocol population.
Between November 20, 2015, and September 30, 2019, 386 patients were randomly assigned, with 194 in the BuFlu group and 192 in the BuCy group. The median follow-up period after random assignment was 55.0 months. The 1-year TRM was 7.2% (95% CI, 4.1 to 11.4) in the BuFlu group and 14.1% in the BuCy group, with a significant difference (95% CI, 9.6 to 19.4; hazard ratio [HR], 0.51; 95% CI, 0.27 to 0.97; P = .041). The 5-year relapse rate was 17.9% in the BuFlu group and 14.2% in the BuCy group (95% CI, 9.1 to 20.5; HR, 1.12; 95% CI, 0.65 to 1.95; P = .670). The 5-year overall survival was 72.5% (95% CI, 62.2 to 80.4) in the BuFlu group and 68.2% (95% CI, 58.9 to 75.9; HR, 0.84; 95% CI, 0.56 to 1.26; P = .465) in the BuCy group (HR 0.84; P = 0.465). Grade 3 regimen-related toxicity (RRT) was significantly lower in the BuFlu group (0%) compared to 4.7% in the BuCy group (P = 0.002). At least one type of grade 3-5 adverse event was reported in 68.1% of patients in the BuFlu group and 77.4% in the BuCy group (P = 0.041).
The BuFlu regimen in haplo-HCT for AML patients demonstrated lower TRM and regimen-related toxicity, with similar relapse rates compared to the BuCy regimen, indicating its potential as a more favorable treatment option.