An all-oral treatment regimen led to complete responses in almost half of all patients with newly diagnosed acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy, according to findings from the phase I/II ASCERTAIN V trial published in The New England Journal of Medicine.
This all-oral combination of decitabine/cedazuridine and venetoclax received approval from the U.S. Food and Drug Administration (FDA) on May 13, 2026, based on findings from the ASCERTAIN V (Study ASTX727-07) trial.
“Having received approval, we anticipate that this oral AML regimen will become the standard of care for patients who are older or more frail,” stated lead author Gail J. Roboz, MD, the William S. Paley Professor in Clinical Medicine and Director of the Clinical and Translational Leukemia Program at Weill Cornell and a hematologist-oncologist at NewYork-Presbyterian/Weill Cornell Medical Center. “We hope these results point to a future for patients [with AML] where the treatment journey is less disruptive and less burdensome without sacrificing outcomes.”
Background and Study Methods
Parenteral administration for azacitidine or decitabine has been challenging for patients with AML as well as for providers, but has been part of the standard-of-care treatment. The oral treatments, however, have demonstrated equivalent pharmacokinetic properties to intravenous administration, although limited survival has been seen with oral decitabine monotherapy.
Investigators conducted an open-label, multicenter, nonrandomized phase I/II trial to assess the benefit of the all-oral treatment regimen. The trial enrolled patients with newly diagnosed AML who were aged 75 or older or who were ineligible for intensive chemotherapy.
“The goal of the all-oral therapy is to keep people out of the hospital, especially once they have achieved remission,” said Dr. Roboz, who is also a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell. “Patients are thrilled not to have to deal with monthly chemotherapy injections or infusions.”
Myelosuppression was observed in phase I, so schedule adjustments were encouraged in phase IIb after bone marrow blast clearance.
Key Findings
A total of 189 patients were enrolled in the study.
No drug–drug interactions were observed between decitabine/cedazuridine and venetoclax.
In the phase IIb portion of the study, complete responses were observed in 47% of patients (95% confidence interval [CI] = 36%–57%), and the rate of complete response/complete response with incomplete hematologic recovery was 63% (95% CI = 53%–73%).
The median overall survival was 15.5 months (95% CI = 7.6 to not estimable).
The most common adverse events of grade 3 or higher were anemia (30%), neutropenia (26%), and febrile neutropenia (25%). At 30 days, the mortality rate was 3%, and 10% at 60 days.
“[Patients with AML] taking ongoing cycles of treatment require close monitoring but can still have an excellent quality of life,” Dr. Roboz said, noting that patients have to receive continuous treatment.
“The goal is to get away from treatment cycles that go on indefinitely,” said Dr. Roboz, explaining that further research is exploring the addition of other agents to potentially prevent continuous treatment. “We want to drive the leukemic cells to such low levels that patients can discontinue therapy and be cured.”
DISCLOSURES: This research was funded by Taiho Oncology, Inc. For full disclosures of the study authors, visit nejm.org.
