FDA Approves Treosulfan as Part of AML/MDS Conditioning Regimen

The FDA approved treosulfan (Grafapex) with fludarabine as a preparative regimen for allogeneic hematopoietic stem cell transplantation in patients ages 1 year and older with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), Medexus announced on Wednesday.

“This FDA approval provides a useful option for adult and pediatric patients, with the potential to enhance overall survival [OS] while minimizing side effects,” said Filippo Milano, MD, PhD, of the Fred Hutch Cancer Center in Seattle, in the company press release.

The regimen was evaluated in MC-FludT.14/L Trial II, which compared treosulfan versus busulfan alongside fludarabine in 570 patients. Eligible patients included adults with AML or MDS, a Karnofsky performance status ≥60%, and age ≥50 years or a hematopoietic cell transplantation comorbidity index score >2.

Compared with busulfan, the hazard ratio for OS was 0.67 (95% CI 0.51-0.90) in favor of treosulfan 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 events included musculoskeletal pain, stomatitis, pyrexia, nausea, edema, infection, and vomiting. Selected grade 3 or 4 non-hematologic laboratory abnormalities were increased gamma-glutamyl transferase, bilirubin, alanine aminotransferase, aspartate aminotransferase, and creatinine.

Previously reported data from the trial showed a 2-year event-free survival rate of 64% in the treosulfan group versus 50.4% in the busulfan group (P

Patients who received treosulfan also had an improved 2-year OS rate (87.5% vs 69%, P=0.0082) and lower rates of transplantation-related mortality (12.1% vs 28.2%, P=0.020) and non-relapse mortality (11.4% vs 22.6%, P=0.053) compared with patients who received busulfan. The 2-year relapse rates were similar between the two groups (24.6% vs 23.3%, respectively, P=0.50).