In a Chinese phase III trial reported in the Journal of Clinical Oncology, Zhang et al found that conditioning with busulfan plus cyclophosphamide (BuCy) was noninferior to total-body irradiation plus cyclophosphamide (TBI-Cy) in 2-year overall survival among adult patients with standard-risk B-cell acute lymphoblastic leukemia (ALL) undergoing HLA-matched allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Study Details
The multicenter open-label trial included 545 evaluable patients (per-protocol population) in first complete remission. They were randomly assigned between January 2016 and February 2020 to receive busulfan at 0.8 mg/kg four times daily on days –7 to –4 and cyclophosphamide at 60 mg/kg once daily on days –3 and –2 (n = 273) or TBI at 4.5 Gy on days –5 and –4 and cyclophosphamide at 60 mg/kg once daily on days –3 and –2 (n = 272) prior to allo-HSCT.
The primary endpoint was 2-year overall survival. Noninferiority of BuCy was shown if the upper limit of the 95% confidence interval (CI) for the difference between TBI-Cy vs BuCy did not exceed 10%.
Key Findings
Overall survival at 2 years was 76.6% (95% CI = 71.7%–81.8%) in the BuCy group vs 79.4% (95% CI = 74.7%–84.4%) in the TBI-Cy group (P = .457; difference = 2.9%, 95% CI = –4.1% to 9.8%, P = .022 for noninferiority), indicating noninferiority of BuCy.
At 2 years, relapse rates were 20.2% (95% CI = 15.6%–25.1%) vs 18.4% (95% CI = 14.0%–23.2%, P = .616) and the nonrelapse mortality was 11.0% (95% CI = 7.6%–15.0%) vs 11.0% (95% CI = 7.7%–15.1%, P = .988).
No significant differences between the BuCy vs TBI-Cy groups were observed in:
- Rates of grade ≥ 3 regimen-related toxicity within 28 days posttransplantation (10.3% vs 9.2%, P = .675)
- Grade ≥ 3 nonhematologic toxicity of any cause within 100 days posttransplantation (64.8% vs 60.0%, P = .237)
- 100-day grade 2 to 4 acute graft-vs-host disease (GVHD; 30.8% vs 27.9%, P =.463; grade 3–4 in 10.6% vs 10.3%, P = .870)
- 2-year chronic GVHD (31.1% vs 28.7%, P = .524)
- Late toxic effects among patients who were disease-free at 6 months posttransplantation (36.4% vs 39.7%, P = .453).
The investigators concluded, “The BuCy regimen has noninferior efficiency and safety as TBI-Cy (4.5 Gy x 2) for patients with adult standard-risk B-cell ALL in first complete remission undergoing HLA-matched allo-HSCT.”
Qifa Liu, MD, of the Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Special Project for Research and Development in Key Areas of Guangdong Province, National Natural Science Foundation of China, National Key Research and Development Projects, and others. For full disclosures of the study authors, visit ascopubs.org.
