Busulfan Plus Cyclophosphamide vs Total Body Irradiation Plus Cyclophosphamide for ALL

Busulfan plus cyclophosphamide demonstrated noninferior efficiency and safety compared with total body irradiation (TBI) plus cyclophosphamide for adult patients with standard-risk B-cell acute lymphoblastic leukemia (ALL) in first complete remission after allogeneic hematopoietic stem-cell transplantation (alloHSCT), according to a phase 3 trial published in the Journal of Clinical Oncology.

“It remains controversial whether busulfan-based vs TBI–based regimens have comparable outcomes in patients with ALL undergoing [alloHSCT],” wrote Haiyan Zhang, MD, Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China, and colleagues.

This open-label, randomized phase 3 trial, performed at 13 hospitals in China, aimed to compare these regimens as conditioning for alloHSCT in patients with B-cell ALL in first complete remission. Patients were randomly assigned in a 1:1 ratio to busulfan plus cyclophosphamide (0.8 mg/kg 4 times per day on days –7 to –4 and cyclophosphamide 60 mg/kg once daily on days –3 to –2) or TBI plus cyclophosphamide (4.5 Gy TBI on days –5 to –4 and cyclophosphamide 60 mg/kg once daily on days –3 to –2). The primary end point was 2-year overall survival (OS).

Between January 2016 and February 2020, 275 patients were assigned to receive busulfan plus cyclophosphamide, and 273 were assessed, while 275 patients were assigned to receive to TBI plus cyclophosphamide, and 272 were assessed. The 2-year OS was 76.6% (95% CI, 71.7 to 81.8) and 79.4% (95% CI, 74.7 to 84.4; P = .457), equating to a difference of 2.9% (95% CI, –4.1 to 9.8; P = .022). This difference indicates noninferiority of busulfan plus cyclophosphamide vs TBI plus cyclophosphamide.

The 2-year relapse was 20.2% (95% CI, 15.6 to 25.1) and 18.4% (95% CI, 14 to 23.2; P = .616), and the nonrelapse mortality was 11% (95% CI, 7.6 to 15) and 11% (7.7 to 15.1; P = .988) in the busulfan plus cyclophosphamide and TBI plus cyclophosphamide groups, respectively. There were no differences in regimen-related toxicity, graft-versus-host disease, or late effects between the 2 groups.

Overall, “The [busulfan plus cyclophosphamide] regimen has noninferior efficiency and safety as TBI [plus cyclophosphamide] (4.5 Gy × 2) for patients with adult standard-risk B-cell ALL in  [first complete remission] undergoing HLA-matched alloHSCT,” the study authors concluded.

Source:

Zhang H, Fan Z, Huang F, et al. Busulfan Plus Cyclophosphamide Versus Total Body Irradiation Plus Cyclophosphamide for Adults Acute B Lymphoblastic Leukemia: An Open-Label, Multicenter, Phase III Trial. J Clin Oncol. Published online September 9, 2022. doi:10.1200/jco.22.00767