Integration of venetoclax into a fludarabine and melphalan conditioning regimen in patients aged 50 years and older with acute myeloid leukemia and myelodysplastic syndrome: Results from a phase 2 clinical trial.

BACKGROUND: The optimal regimens for older adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain uncertain.

METHODS: The authors conducted a multicenter phase 2 trial to evaluate the novel venetoclax, fludarabine, and melphalan (VFM) regimen in patients with AML or MDS aged 50 years and older. The VFM regimen consisted of venetoclax (400 mg daily on days -8 to -2), fludarabine (30 mg/m2 daily on days -7 to - 3), and melphalan (120-140 mg/m2 daily on day -2).

RESULTS: Sixty patients (median age, 58 years; age range, 51-66 years) received the novel VFM conditioning regimen. The 2-year disease-free survival (DFS) rate was 75.0% (95% confidence interval [CI], 64.8%-86.8%), which was the primary end point. Two-year rates of overall survival, graft-versus-host disease (GVHD)-free and recurrence-free survival, nonrelapse mortality, and relapse were 78.3% (95% CI, 68.6%-89.5%), 61.6% (95% CI, 50.5%-75.3%), 13.3% (95% CI, 6.1%-23.3%), and 11.7% (95% CI, 5.1%-21.3%), respectively. Treatment-related grade 2-3 nonhematologic adverse events occurred in 58% of patients, with no grade 4-5 nonhematologic toxicities. The cumulative incidence of grade 2-4 and grade 3-4 acute GVHD at day 100 was 5.0% (95% CI, 1.3%-12.7%) and 1.7% (95% CI, 0.1%-7.9%), respectively. The 2-year cumulative incidence of moderate-to-severe chronic GVHD was 16.7% (95% CI, 8.5%-27.3%).

CONCLUSIONS: These findings support the feasibility of incorporating venetoclax into a fludarabine and melphalan conditioning regimen in older adults with AML/MDS. Notably, the low rates of GVHD and relapse associated with this venetoclax-based conditioning regimen support further study of this platform [ClinicalTrials.gov Identifier: NCT05084027].