FDA approves Treosulfan-Grafapex plus fludarabine as a preparation for adult and pediatric patients with acute myeloid leukemia or MDS undergoing allogeneic hematopoietic stem cell transplantation

On January 21, 2025, the U.S. Food and Drug Administration (FDA) approved Treosulfan (Treosulfan)-Grafapex in combination with fludarabine as an allogeneic Preparatory program for hematopoietic stem cell transplantation (alloHSCT) for patients 1 year old and older with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). This approval provides adult and pediatric patients with new treatment options to improve transplant success. Trioxovan is an alkylating agent, and its combined use with fludarabine is designed to create an optimal in vivo environment for hematopoietic stem cell transplantation, thereby improving the therapeutic effect.

In terms of efficacy and safety,MC-FludT.14/L Trial II (NCT00822393) evaluated the combination of trioxofan withBusulfan and fludarabine. The randomized active-controlled trial enrolled 570 eligible patients, aged 18-70 years, with AML or MDS. Patients must have a Karnofsky functional status ≥60%, or be ≥50 years old and have a Hematopoietic Cell Transplant Comorbidity Index (HCTCI) score >2. Participants were randomly assigned to the Trioxofan group (280 people) or the Busulfan group (290 people).

The primary efficacy outcome measure is overall survival (OS), which is the time from randomization to death from any cause. The results showed that compared with Busulfan, the OS hazard ratio of the trioxofan group was 0.67 (95% CI: 0.51, 0.90), 0.73 (95% CI: 0.51, 1.06) in AML patients, and 0.64 (95% CI: 0.40, 1.02) in MDS patients, showing a significant survival advantage.

Regarding the recommended dosage, the administration schedule of trioxovan is 10g/m² per day on days 4, 3 and 2. At the same time, the dose of fludarabine is 30mg/m² per day, and the administration time is day 6, day 5, day 4, day 3 and day 2, and allogeneic hematopoietic stem cell infusion is performed on day 0. This treatment plan can effectively improve the prognosis of patients and help them recover after transplantation. In terms of adverse reactions, the most common ones include musculoskeletal pain, stomatitis, fever, nausea, edema, infection and vomiting, with an incidence rate of ≥20%. In addition, selected grade 3 or 4 non-hematologic laboratory abnormalities included increases in GGT, bilirubin, ALT, AST, and creatinine.

Reference materials:https://www.drugs.com/grafapex.html