Defining a Therapeutic Window for Venetoclax in Post-Transplant Maintenance Therapy for High-Risk Acute Myeloid...

Patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) continue to face a substantial risk of relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which remains a leading cause of treatment failure. In our previous study, maintenance therapy with a combination of venetoclax and decitabine has shown potential in reducing relapse rates; however, its efficacy and safety, particularly in relation to drug concentration levels, are not yet fully elucidated. This study aimed to evaluate the influence of venetoclax blood concentrations on the efficacy and toxicity of venetoclax plus decitabine as maintenance therapy in high-risk AML/MDS patients after allo-HSCT. We retrospectively analyzed clinical data from 58 high-risk AML/MDS patients who received this maintenance regimen at our center between April 2018 and June 2023, with a focus on the association between venetoclax blood levels, treatment response, and adverse effects. The results demonstrated that the venetoclax-decitabine maintenance regimen was effective and generally well-tolerated, improving remission rates without significantly increasing intolerable toxicities or the risk of graft-versus-host disease (GVHD). Notably, substantial interindividual variability in venetoclax blood concentrations was observed. Patients with concentrations maintained within the range of 2605-4060 ng/mL achieved superior outcomes and higher safety profiles. In conclusion, this study provides key evidence for establishing a target concentration window for venetoclax, highlighting the importance of therapeutic drug monitoring in guiding post-transplant maintenance therapy for high-risk AML/MDS patients.