FDA Approves Treosulfan Regimen For Preparative Use in Stem Cell Transplantation Patients With AML, MDS

Author(s):

Luke Halpern, Assistant Editor

Key Takeaways

Treosulfan, combined with fludarabine, is approved for alloHSCT in patients with AML or MDS aged one year and older.
The approval is supported by results from a randomized trial comparing treosulfan with busulfan and fludarabine.
The new regimen aims to enhance overall survival and reduce side effects, benefiting both adult and pediatric patients.

The FDA approved treosulfan, in combination with fludarabine, for patients 1 year of age and older with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).

The FDA approved treosulfan (Grafapex; Medexus Pharma) in combination with fludarabine (Fludara; Bayer HealthCare Pharmaceuticals) as a preparative regimen for allogeneic hematopoietic stem cell transplantation (alloHSCT) in adult and pediatric patients 1 year and older with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), according to a news release from Medexus Pharma.¹

Blast cell in Acute myeloid leukemia from human blood cells (White blood cells cancer , Bone marrow aspirate)

Treosulfan can become an effective option for both adults and pediatrics with hematological malignancies. | Image Credit: © Pichitchai | stock.adobe.com

"This FDA approval provides a useful option for adult and pediatric patients, with the potential to enhance overall survival while minimizing side effects," Filippo Milano, MD, principal investigator in clinical trials utilizing treosulfan as a part of a conditioning regimen, said in the news release.¹

Approval of treosulfan is based in part on strong study results from the MC-FludT.14/L Trial II (NCT00822393), a randomized, active-controlled trial comparing treosulfan and the combination of busulfan (Myleran; GlaxoSmithKline) and fludarabine as a preparative regimen for alloHSCT.²

The trial, which enrolled 570 patients, randomized patients to treosulfan (n = 280) or busulfan (n = 290) to investigate the primary efficacy outcome of overall survival (OS). Stratified by donor type and risk group, the hazard ratio (HR) for OS compared with busulfan was 0.67 (95% 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, according to the news release.¹

Common adverse reactions that patients reported were musculoskeletal pain, pyrexia, nausea, edema, and infection. There were some select grades 3 or 4 nonhematological laboratory abnormalities, including increased gama-glutamyl transferase and increased creatine.¹

About the Trial

Trial Name: Clinical Phase III Trial Treosulfan-based Conditioning Versus Reduced-intensity Conditioning (RIC)

ClinicalTrials.gov ID: NCT00822393

Sponsor: medac GmbH

Completion Date: January 25, 2018

In a final confirmatory analysis of the trial, the median follow-up was 15.4 months for patients treated with treosulfan and 17.4 months for patients treated with busulfan. In the treosulfan cohort, 2-year event-free survival was 64.0% (95% CI, 56.0-70.9), and it was 50.4% (95% CI, 42.8-57.5) in the busulfan group. Frequent adverse events (AEs) were abnormal blood chemistry results and gastrointestinal disorders, while minimal serious AEs were reported. The investigators deemed treosulfan as non-inferior to busulfan when as a conditioning regimen for alloHSCT in comorbid or older patients with AML or MDS.³

Treosulfan has been investigated and found to be effective for other patient populations, namely myelofibrosis (MF). In a recent trial, treosulfan conditioning demonstrated improved progression-free survival and non-relapse mortality compared with busulfan conditioning prior to alloHSCT in patients with MF. Patients who received treosulfan conditioning had a significantly higher OS and superior capabilities in PFS than those who received busulfan conditioning.⁴

The preparative treatment’s success in extending OS in other hematological conditions is a positive sign for its efficacy not only in AML and MDS, but in other forms of leukemia. Pharmacists should be aware of the benefits of treosulfan conditioning in patients with AML or MDS and be prepared to recommend it as a potential option prior to alloHSCT.^1,4

REFERENCES

1. Medexus Pharma. Medexus announces FDA approval of GRAFAPEX (treosulfan) for injection and provides business update. News Release. Released January 22, 2025. Accessed January 22, 2025. https://www.medexus.com/en_US/investors/news-events/press-releases/detail/176/medexus-announces-fda-approval-of-grafapex-treosulfan-for

2. ClinicalTrials.gov. Clinical phase III trial treosulfan-based conditioning versus reduced-intensity conditioning (RIC). National Library of Medicine. Last Updated July 30, 2020. Accessed January 22, 2025. https://clinicaltrials.gov/study/NCT00822393

3. 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. Lancet Haematol. 2020;7(1):e28-e39. doi:10.1016/S2352-3026(19)30157-7.

4. Gerlach A. Treosulfan improves survival and lowers mortality prior to allo-HSCT in patients with myelofibrosis. Pharmacy Times. Published October 7, 2024. Accessed January 22, 2025. https://www.pharmacytimes.com/view/treosulfan-improves-survival-lowers-mortality-prior-to-allo-hsct-in-patients-with-myelofibrosis