On 21 January 2025, the US Food and Drug Administration (FDA) approved treosulfan (Grafapex, medac GmbH), an alkylating agent, with fludarabine as a preparative regimen for allogeneic haematopoietic stem cell transplantation (alloHSCT) in adult and paediatric patients 1 year of age and older with acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS).
Efficacy was evaluated in MC-FludT.14/L Trial II (NCT00822393), a randomised active-controlled study comparing treosulfan to busulfan with fludarabine as a preparative regimen for allogeneic transplantation. Eligible patients included adults 18 to 70 years old with AML or MDS, Karnofsky performance status ≥ 60%, and age ≥ 50 years or haematopoietic cell transplantation comorbidity index score > 2. There were 570 patients randomised to treosulfan (n=280) or busulfan (n=290).
The major efficacy outcome measure was overall survival (OS), defined as the time from randomisation until death from any cause. The hazard ratio for OS (stratified by donor type and risk group) compared to busulfan was 0.67 (95% confidence interval [CI] 0.51, 0.90) in the randomised population, 0.73 (95% CI 0.51, 1.06) in patients with AML and 0.64 (95% CI 0.40, 1.02) in patients with MDS.
The most common adverse reactions (≥20%) were musculoskeletal pain, stomatitis, pyrexia, nausea, oedema, infection, and vomiting. Selected Grade 3 or 4 non-haematological laboratory abnormalities were increased GGT, increased bilirubin, increased ALT, increased AST, and increased creatinine.
The recommended treosulfan dose is 10 g/m2 daily on days -4, -3, and -2 in combination with fludarabine 30 mg/m2 daily on days -6, -5, -4, -3, and -2, and allogeneic haematopoietic stem cell infusion on day 0.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA’s Oncology Center of Excellence Project Facilitate.