All-Oral Treatment Strategy May Reduce Treatment Burden in Acute Myeloid Leukemia

Clinical Summary:

• Gail Roboz, MD, discusses results from the phase 1/2 ASCERTAIN-V trial evaluating all-oral decitabine and cedazuridine plus venetoclax in older patients with acute myeloid leukemia (AML) and selected younger patients ineligible for intensive chemotherapy.
• The all-oral regimen demonstrated encouraging remission and survival outcomes, with manageable myelosuppression requiring careful bone marrow monitoring and individualized venetoclax dose modifications.
• These findings support further evaluation of all-oral treatment strategies for patients with AML, particularly in the post-remission setting where reduced infusion center visits and individualized dosing may improve treatment convenience and quality of life.

Gail Roboz, MD, Weill Cornell Medicine and New York-Presbyterian Hospital, New York, New York, discusses results from the phase 1/2 ASCERTAIN-V trial evaluating all-oral decitabine and cedazuridine plus venetoclax in patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy following her presentation at the Lymphoma, Leukemia & Myeloma Congress in New York, New York. 

Dr Roboz reviews the clinical activity and safety of the all-oral combination, including strategies for managing myelosuppression through bone marrow monitoring and venetoclax dose modifications. She also discusses its potential to reduce transplant burden, improve patient convenience, and support outpatient management of AML. 

Transcript:

Hi everyone my name is Dr Gail Roboz, I'm a professor of medicine and director of the leukemia program at Weill Cornell Medicine and the New York Presbyterian Hospital in New York City. 

I am recording live from the exciting LL&M 2026 Congress, where I have the pleasure and privilege of chairing the Leukemia Day. We are fresh out of the AML session, during which I took the opportunity to present some data and discuss a recently published all-oral regimen for AML. 

AML is a very difficult disease, and for many decades, we have been used to intensive chemotherapy backbones requiring very, very long hospitalization for most of our patients. 

Older patients typically can't handle that type of very intensive therapy and for years since the publication of the VIALE-A regimen, the combination of a hypomethylating agent and venetoclax has been the standard of care for the treatment of older patients with AML and also some younger patients who had comorbidities or other reasons why they couldn't get intensive therapy. 

Now AML induction is still treating AML, which is a difficult disease, but we have learned how to do this more safely and in trying to push the envelope for patients requiring ongoing post-remission cycles, it really became an incredible goal to try to see whether we could move this treatment into the all-oral setting.

I had the privilege of leading a trial called ASCERTAIN-V, which was the combination of oral decitabine and cedazuridine with venetoclax, in the same treatment population as what established this standard of care. These are older patients, as well as selected younger ones with multiple comorbidities. In this trial, we combined oral decitabine and cedazuridine with an initial ramp-up of venetoclax followed by 28-day cycles, but I'll caveat that right away by saying that in the post-remission setting, patients didn't typically get 28 full days for many cycles. 

The point of the regimen was to try to mirror what we saw in VIALE-A, and these patients ended up with a CR CRI rate of 63%, a CR rate of 47%, and actually in the pivotal Phase IIb study they had overall survival of 15 and a half months, which is really tracking with what our expectations would be for that group of patients with this type of a regimen. Not a randomized trial, so the ASCERTAIN-V trial was a phase 1/2a, and then 2b trial looking initially at safety and then at efficacy in the pivotal group. But we were very pleased to see the tracking with the expected outcomes, with the safety signal being primarily expected myelosuppression.

But here's where we did something good, which was to do a lot of bone marrow biopsies to try to figure out how to get patients safely through this regimen for as many cycles as possible. The idea is to clear blasts, do a bone marrow biopsy demonstrating blast clearance, and then in the post-remission setting have decreased number of days of venetoclax so that quite few patients in cycle 3 and beyond were getting anywhere near 28 days. This is outlined in the New England Journal of Medicine manuscript, and I actually showed, both on stage and in the manuscript, a chart to try to help doctors figure out how to modify those doses to try to mitigate post-remission myelosuppression.

It's a myelosuppressive regimen, so counts do need to be watched. We always have to watch for drug-drug interactions and the main thing about this is that I think that with the careful dosing guidelines, what we are seeing already is really happy patients who are able to do this in the outpatient setting without having to trek into the hospital or the infusion center so frequently. I really do think that for many patients, this is a quality-of-life benefit that has already been shown in my clinic to be incredibly important. 

Now as we go forward, and I discussed this a little bit in the presentation, what is the role for all-oral therapy in the future? How do we incorporate the convenience and quality of life improvements? I think primarily this is going to be true in the post-remission setting, but we need more data to find out how the regimen is doing in terms of adherence and safety now that it's in the real world and how patients are responding.