FDA approves treosulfan with fludarabine as a preparative regimen for alloHSCT in adult and pediatric patients with AML or MDS

FDA approval (Feb 6, 2025)

The FDA approved treosulfan (Grafapex; medac GmbH), an alkylating agent, in combination with fludarabine as a preparative regimen for allogeneic hematopoietic stem cell transplantation (alloHSCT) in adult and pediatric patients aged ≥1 year with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).

Supporting evidence

Efficacy and safety were evaluated in MC-FludT.14/L Trial II (NCT00822393), a randomized active-controlled study comparing treosulfan vs busulfan, each with fludarabine, as transplant preparative regimens.

Eligible patients included adults 18–70 years with AML or MDS, Karnofsky performance status ≥60%, and age ≥50 years or hematopoietic cell transplantation comorbidity index (HCTCI) >2. A total of 570 patients were randomized (treosulfan n=280; busulfan n=290).

The major efficacy outcome was overall survival (OS) (time from randomization to death). OS hazard ratios (treosulfan vs busulfan; stratified by donor type and risk group) were:

• Randomized population: 0.67 (95% CI, 0.51–0.90)
• AML subgroup: 0.73 (95% CI, 0.51–1.06)
• MDS subgroup: 0.64 (95% CI, 0.40–1.02)

Safety

Most common adverse reactions (≥20%) were musculoskeletal pain, stomatitis, pyrexia, nausea, edema, infection, and vomiting. Selected grade 3/4 nonhematologic lab abnormalities included increased GGT, bilirubin, ALT, AST, and creatinine.

Dosing (label)

Treosulfan 10 g/m² daily on days −4, −3, −2, with fludarabine 30 mg/m² daily on days −6 to −2, and stem cell infusion on day 0.