FDA approves treosulfan plus fludarabine as an allo-HSCT preparative regimen in patients with AML or MDS

On January 22, 2025, the U.S. Food and Drug Administration (FDA) granted approval to treosulfan, an alkylating agent, in combination with fludarabine as a preparative regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adult and pediatric patients aged >1 year with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS).¹

The approval was based on findings from the randomized, active-controlled, MC-FludT.14/L trial II (NCT00822393) of treosulfan vs busulfan as a preparative regimen for allo-HSCT in combination with fludarabine.¹ A total of 570 patients randomized to treosulfan (n = 280) or busulfan (n = 290) were included.¹

• Treatment with treosulfan provided survival benefits over busulfan with hazard ratios for OS (stratified by donor type and risk group) of 0.73 (95% confidence interval [CI], 0.51–1.06) in patients with AML and 0.64 (95% CI, 0.40–1.02) in patients with MDS.¹
• The most common adverse reactions occurring in ≥20% of patients were musculoskeletal pain, stomatitis, pyrexia, nausea, edema, infection, and vomiting. Selected Grade 3/4 nonhematologic laboratory abnormalities were elevated levels of gamma-glutamyl transferase, bilirubin, alanine aminotransferase, aspartate aminotransferase, and creatinine.¹

The recommended dose of treosulfan is 10 g/m² once daily on Days −4, −3, and −2, alongside fludarabine 30 mg/m² once daily on Days −6, −5, −4, −3, and −2 of allo-HSCT infusion on Day 0.¹