Venetoclax-Based Conditioning Regimen Prior to Allo-HSCT for Older Patients With Acute Myeloid Leukemia and Myelodysplastic Syndromes

Clinical Summary:

• Design/Population: This multicenter phase 2 trial evaluated the addition of venetoclax to fludarabine and melphalan conditioning before allogeneic hematopoietic stem cell transplantation in patients aged 50 years and older with acute myeloid leukemia or myelodysplastic syndrome.
• Key Outcomes: The venetoclax-based conditioning regimen was associated with encouraging 2-year disease-free and overall survival, low relapse and non-relapse mortality, and a favorable safety profile. 
• Clinical Relevance: These findings support the feasibility of incorporating venetoclax into conditioning regimens before allogeneic transplantation in older adults with with acute myeloid leukemia or myelodysplastic syndromes.

Results from a phase 2 study demonstrated that incorporating venetoclax into a fludarabine and melphalan conditioning regimen before allogeneic hematopoietic stem cell transplantation (allo-HSCT) produced encouraging survival outcomes among older adult patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). 

“Several clinical trials have demonstrated that venetoclax was feasible and safe when incorporated into conditioning regimens before transplantation for high-risk myeloid malignancies,” stated Xiaoyu Lai, PhD, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China, and coauthors. “However, only a limited number of studies have investigated venetoclax-based conditioning regimens in older adults.” 

In this multicenter, single-arm study, 60 patients aged 50 years and older with AML or MDS received a conditioning regimen consisting of 400 mg of daily venetoclax on (days −8 to −2) plus 30 mg/m² of daily fludarabine (on days −7 to −3) and 120 to 140 mg/m²  of melphalan (on day −2) before allo-HSCT. The primary end point was 2-year disease-free survival (DFS). Key secondary end points included overall survival (OS), graft-versus-host disease (GVHD)-free and relapse-free survival, relapse, non-relapse mortality, and safety.

 At 2 years, the DFS rate was 75%. The 2-year OS rate was 78.3%, while GVHD-free and relapse-free survival  was 61.6%. The cumulative incidence of non-relapse mortality and relapse were 13.3% and 11.7%, respectively. 

Treatment-realted grade 2/3 nonhematologic adverse events were reported in 58% of patients. No grade >3 nonhematologic toxicities were reported. 

The cumulative incidence of grade 2/4 acute GVHD at day 100 was 5%, including grade 3/4 acute GVHD in 1.7% of patients. The 2-year cumulative incidence of moderate-to-severe chronic GVHD was 16.7%. 

“These findings support the feasibility of incorporating venetoclax into a fludarabine and melphalan conditioning regimen in older adults with AML or MDS,” concluded Dr Lai et al. “Notably, the low rates of GVHD and relapse associated with this venetoclax-based conditioning regimen support further study of this platform.”

Source:

Lai X, Zhu P, Yang L, et al. 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. Cancer. Published online: May 20, 2026. doi:10.1002/cncr.70467