Ruxolitinib and Decitabine With Modified Busulfan/Cyclophosphamide Conditioning Treatment Tolerable, Reduces Relapse for High-Risk AML/MDS

Ruxolitinib and decitabine in combination with modified busulfan/cyclophosphamide (Rux-Dec-mBu/Cy) demonstrated promising relapse reduction and survival outcomes among patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome with increased blasts (MDS-IB) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), according to study results published in Frontiers in Immunology. 

Following allo-HSCT, approximately 40% to 50% of patients with high-risk AML or MDS-IB experience relapse. A combination of ruxolitinib, a JAK1/JAK2 inhibitor, and a dec-mBu/Cy regimen has demonstrated efficacy for the treatment of AML and MDS. Researchers conducted a prospective phase 2 study to evaluate the safety and tolerability, as well as the efficacy, in an expanded cohort analysis.

The primary end point was 2-year cumulative incidence of relapse, while secondary endpoints included incidence rate of engraftment (+ 30 days), active graft-versus-host disease (GVHD; +100 days), chronic GVHD (2-year), 2-year non-relapse mortality (NRM), 2-year disease-free survival (DFS), 2-year GVHD-free, relapse-free survival (GRFS), and 2-year overall survival (OS).

Overall, 58 patients with high-risk AML or MDS were included and treated with ruxolitinib and dec-mBu/Cy. Most patients were male (75.9%) and the median age among all patients was 45 (range, 15 to 47) years. Ruxolitinib was administered from day -15 to -1 and decitabine from day -15 to -10, followed by mBu/Cy conditioning and allo-HSCT.

The 2-year cumulative incidence of relapse was 19.0% (95% confidence interval [CI], 10.1 to 30.0). Additionally, the 2-year NRM was 10.5% (95% CI, 4.2 to 20.0). The median follow-up was 967 (range, 464 to 1597) days and the 2-year OS was 70.3% (95% CI, 56.6 to 80.4). The 2-year DFS probability was 70.6% (95% CI, 57.0 to 80.6), as well as a 2-year GRFS probability of 65.2% (95% CI, 51.4 to 76.0). All patients achieved neutrophil engraftment.

In terms of safety, the most common grade ≥3 adverse event being oropharyngeal mucositis (8.6%) and the most common infection was lung infections (24.2%). Additionally, grade 2 to 4 acute GVHD occurred in 44.1% (95% CI, 29.8 to 57.5) of patients. Chronic GVHD at 2 years was found among 14.1% (95% CI, 1.5 to 13.7) of patients.

The researchers concluded, “our study indicates that the Rux-Dec-mBu/Cy regimen, may be an option for patients with high-risk AML/MDS undergoing allo-HSCT.”

They added, “The findings from our study could inform the planning of allogeneic HSCT strategies for individuals with high-risk AML/MDS.”

Source:

Wei Y, Luan S, Wang L, et al. Ruxolitinib and decitabine plus a busulfan–cyclophosphamide conditioning regimen for relapse prophylaxis in patients with high-risk acute myeloid leukemia or myelodysplastic syndromes. Frontiers in Immunology. Published online August 17, 2025. doi:10.3389/fimmu.2025.1586512