New Study Supports Venetoclax and Decitabine as AML Treatment Standard

A recent study presented at the European Hematology Association Congress 2025 indicates that the oral combination of venetoclax (Venclexta) and decitabine/cedazuridine may establish a new standard of care for patients with newly diagnosed acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy. The ASCERTAIN-V trial (NCT04975919) showcased promising results, where significant response rates were observed among participants who received this all-oral regimen, particularly benefiting older patients and those with comorbidities that preclude traditional treatment options.

Dr. Gail J. Roboz, MD, a professor of medicine and director of the Clinical and Translational Leukemia Program at Weill Cornell Medicine, emphasized the significance of these findings, stating, "For newly diagnosed patients with AML ineligible for intensive chemotherapy, the all-oral regimen of decitabine and venetoclax represents a potential new standard of care for these patients."

The ASCERTAIN-V trial included multiple phases: Phase 1 (n = 30), Phase 2A (n = 58), and Phase 2B (n = 101). The study reported complete response (CR) rates of 40.0% in Phase 1, 37.9% in Phase 2A, and 46.5% in Phase 2B. Additionally, the rate of complete response with incomplete hematologic recovery (CRi) varied across phases, with figures reaching up to 27.6% in Phase 2A. The data suggests that the combination treatment not only elicits responses but also yields encouraging survival outcomes, with median overall survival (OS) rates reported at 14.5 months in Phase 2A and 15.5 months in Phase 2B.

Efficacy comparisons were drawn to previously established treatments involving parenteral formulations. According to Dr. Roboz, while the oral regimen showed comparable safety and efficacy to parenteral azacitidine and venetoclax, it presents a significant advantage in terms of patient convenience and adherence. This observation is particularly pertinent given the treatment burden associated with intravenous therapies.

The trial's findings are underscored by the urgent need for effective treatments for older AML patients, a demographic often sidelined due to the risks associated with intensive chemotherapy. According to the American Cancer Society, the median age of diagnosis for AML is 68 years, highlighting the necessity for accessible and less intensive treatment options for this population.

The ASCERTAIN-V trial methodology involved a nonrandomized interventional design, focusing on an open-label approach to evaluate the safety and efficacy of the all-oral regimen. The pharmacokinetic studies revealed no significant drug-drug interactions between decitabine/cedazuridine and venetoclax, fulfilling the primary study endpoints and enabling further exploration of dosing strategies.

Adverse events were prevalent, with 100% of participants reporting some form of treatment-related adverse events (TRAEs). The most common TRAEs included anemia, neutropenia, and gastrointestinal symptoms. Notably, the study reported a 30-day mortality rate of 3.0%, which reflects the complexities involved in treating this patient population.

Dr. Roboz pointed out the importance of ongoing research to standardize methodologies for evaluating minimal residual disease (MRD) status, as achieving MRD negativity has been shown to correlate with better survival outcomes.

Given the promising results from the ASCERTAIN-V trial, there is growing optimism that the combination of venetoclax and decitabine/cedazuridine could represent a paradigm shift in the treatment of AML, particularly for patients who are deemed ineligible for traditional chemotherapy. As the oncology community awaits further data from ongoing studies, these findings may pave the way for broader adoption of this oral regimen as a frontline treatment for AML, potentially improving outcomes for a vulnerable patient population.

In conclusion, the ASCERTAIN-V trial's results bring forth a significant advancement in the treatment landscape of AML, highlighting the necessity for continued exploration of innovative therapeutic strategies that enhance patient quality of life while improving clinical outcomes.