FDA Approves Treosulfan With Fludarabine for Patients With AML or MDS Prior to AlloHSCT

The US Food and Drug Administration (FDA) has approved treosulfan with fludarabine as a preparative regimen for allogeneic hematopoietic stem cell transplantation (alloHSCT) for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) on January 21, 2025. This approval was based on results from the phase 3 MC-FludT.14/L Trial II.

In this open-label, randomized, non-inferiority trial, 476 patients with AML or MDS who were considered high risk for standard myeloablative preparative regimens were randomized 1:1 to busulfan therapy (n=240) or reosulfan therapy (n-221) along with fludarabine prior to alloHSCT, the primary end point was event-free survival 2 years after alloHSCT among patients with AML or MDS.

Median follow up was shorter for the treosulfan group than the busulfan group (15.4 vs 17.4). Additionally, event-free survival at 2 years post alloHSCT was higher among patients treated with treosulfan than busulfan (64.0%; 95% confidence interval [CI], 56.0 to 70.9 vs 50,4%; 95% CI, 42.8 to 57.5; HR, 0.65; 95% CI, 0.47 to 0.90; p<0·0001 for non-inferiority, p=0·0051 for superiority).

In terms of safety, grade 3 or higher adverse events including abnormal blood counts occurred in 15% of both treatment groups. Serious adverse events were reported slightly higher in the treosulfan group (8%) than the busulfan group (7%).

“Treosulfan was non-inferior to busulfan when used in combination with fludarabine as a conditioning regimen for allogeneic HSCT for older or comorbid patients with acute myeloid leukaemia or myelodysplastic syndrome,” the researchers concluded, “the improved outcomes in patients treated with the treosulfan-fludarabine regimen suggest its potential to become a standard preparative regimen in this population.”

Sources:

Beelen DW, Trenschel R, Stelljes M, et al. Treosulfan or busulfan plus fludarabine as conditioning treatment before allogeneic haemopoietic stem cell transplantation for older patients with acute myeloid leukaemia or myelodysplastic syndrome (MC-FludT.14/L): a randomised, non-inferiority, phase 3 trial. The Lancet Haematology. 2020;7(1):e28-e39. doi: 10.1016/s2352-3026(19)30157-7

FDA approves treosulfan with fludarabine as a preparative regimen for alloHSCT in adult and pediatric patients with AML or MDS. Press Release. The US Food and Drug Administration. Published online February 6, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-treosulfan-fludarabine-preparative-regimen-allohsct-adult-and-pediatric-patients-aml-or?utm_medium=email&utm_source=govdelivery