On January 21, the U.S. Food and Drug Administration (FDA) approved treosulfan (Grafapex), an alkylating agent, with fludarabine as a preparative regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in adult and pediatric patients 1 year of age and older with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).
Efficacy and Safety
Efficacy was evaluated in MC-FludT.14/L Trial II (ClinicalTrials.gov identifier NCT00822393), a randomized active-controlled trial 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 hematopoietic cell transplantation comorbidity index score > 2. There were 570 patients randomly assigned to receive treosulfan (n = 280) or busulfan (n = 290).
The major efficacy outcome measure was overall survival, defined as the time from random assignment until death from any cause. The hazard ratio for overall survival (stratified by donor type and risk group) compared to busulfan was 0.67 (95% confidence interval [CI] = 0.51–0.90) in the randomized 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 (occurring in ≥ 20% of patients) were musculoskeletal pain, stomatitis, pyrexia, nausea, edema, infection, and vomiting. Selected Grade 3 or 4 nonhematologic laboratory abnormalities were increased gamma-glutamyl transferase, bilirubin, alanine aminotransferase, aspartate aminotransferase, and creatinine.
Recommended Dose
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 hematopoietic stem cell infusion on day 0.
