At the 44th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT), Dietrich W. Beelen from the University Hospital of Essen, Essen, DE, presented interim data from the prospective open-label, multi-center phase III randomized study (NCT00822393), which is comparing the safety and efficacy of Treosulfan-based conditioning therapy with reduced intensity to busulfan-based conditioning in adult patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).
The main objective of this phase III study was to demonstrate at least non-inferiority in event‑free survival (EFS) of the Treosulfan-based regimen as compared to the reduced-intensity busulfan-based regimen within 24 months after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The study also aims to compare the associated safety profiles of these two regimens.
In total, 476 patients (median age = 60 years) with AML or MDS in complete remission indicated for matched related donor (MRD) or matched unrelated donor (MUD) allo-HSCT were enrolled in this study and randomly assigned 1:1 to receive either intravenous (IV) treosulfan (10 g/m²/day [d‑4 to d‑2]) or IV busulfan (4 x 0.8 mg/kg/day [d‑4 to d‑3]), both in combination with IV fludarabine (30 mg/m²/day [d-6 to d-2]). After exclusion of patients that were not treated, an overall of 240 patients (median age = 61 years, range 31–70) were enrolled in the busulfan arm and 220 patients (median age = 60 years, range 37–70) in the treosulfan arm.
Key findings in evaluable patients (n = 460):
- 2-year EFS in patients administered treosulfan based conditioning was significantly non‑inferior compared to patients in the busulfan group: 64.0% vs 50.4%, HR = 0.65, P = 0.000016
- 2-year overall survival in patients in the treosulfan and busulfan group: 71.3% vs 56.4%, HR = 0.61, P = 0.0082
- 2-year chronic GvHD- and relapse-free survival rate in patients in the treosulfan and busulfan group: 52.3% vs 38.5%, HR = 0.69, P = 0.0108
- 2-year transplantation-related mortality rate in patients in the treosulfan and busulfan group: 12.1% vs 28.2%, HR = 0.54, P = 0.0201
- 2-year relapse/progression rate in patients in the treosulfan and busulfan group: 24.6% vs 23.3%, HR = 0.87, P = 0.5017
- 100-day grade II–IV acute graft versus host disease (GvHD) in patients in the treosulfan and busulfan group: 6.4% vs 9.6%, P = 0.2099
The speaker, Dietrich Beelen, concluded that the findings of this study demonstrate the non-inferiority of the modified treosulfan (3 x 10 g/m2) /fludarabine (5 x 30 mg/m2) regimen compared to the RIC busulfan/fludarabine regimen for elderly or comorbid AML and MDS patients. Additionally, the clinical outcomes observed in this study “were consistently in favor of the treosulfan/fludarabine regimen thus confirm a major clinical benefit of this regimen as compared to the RIC busulfan/fludarabine regimen in this selected patient population”.
As a result of this interim data and the statistically proven non-inferiority of the treosulfan conditioning regimen, the phase III randomized study was terminated prematurely.