Oral Therapy Enables At-Home Treatment for Acute Myeloid Leukemia

For years, treatment of older patients with acute myeloid leukemia—an aggressive cancer of the blood and bone marrow—has required injections administered in a clinic for five to seven consecutive days each month in addition to an oral pill. For these older patients, that clinic cadence can be quite intensive.

Now, a new all-oral therapy could allow patients to receive treatment at home, saving them the time and effort of traveling to the clinic. A study published June 3 in the New England Journal of Medicine shows how the two pill-based regimen is comparable to traditional injection-based treatments in its effectiveness.

The regimen has now been approved by the United States Food and Drug Administration (FDA) for this patient population based on the results of the study.

“This is the first time ever we have a combination of oral therapies to treat older patients with acute myeloid leukemia who are newly diagnosed,” says Amer M. Zeidan, MD, professor of medicine (hematology) at Yale School of Medicine, chief of the Division of Hematologic Malignancies at Yale Cancer Center, and co-first author of the study. “The main finding of our study is that we have replaced standard injection with a pill.”

While injectable treatments improve patients’ survival, they require patients to visit a clinic five to seven days every month. “They are spending more than a quarter of their remaining life coming to the clinic to get injections,” says Zeidan. “For many seniors, this time toxicity is so disruptive to their quality of life that some choose to forgo treatment entirely.”

To solve this, Zeidan and his colleagues conducted the ASCERTAIN-V Phase I–II clinical trial, which included 189 patients who were 75 or older or had health conditions that made intensive chemotherapy unfavorable. The trial swapped the traditional injection for two oral pills: a combination of decitabine (a chemotherapy that slows cancer growth and boosts production of healthy blood cells) and cedazuridine (an ingredient that allows decitabine to work in a pill form) as well as venetoclax, an inhibitor that blocks a protein cancer cells need to live.

Once a patient’s bone marrow was clear of cancer, the team shortened the number of days the pills were taken in the next cycles. Ventoclax was shortened from 28 days per cycle down to 21, 14, or seven days depending on how quickly a patient's blood count could recover. Decitabine-cedazuridine was shortened from five days per cycle to three to four days.

“This truncation strategy allowed the patients' healthy blood counts to recover faster and remain in good levels for longer periods,” says Zeidan. “It also reduced the risk of dangerous side effects like infections or bleeding while still keeping the leukemia under control.”

In the trial, 47% of patients achieved a complete response—meaning no detectible signs of cancer remained—following the all-oral regimen. Additionally, 63% of patients saw a significant clinical response, and 60% of those who originally needed regular blood or platelet transfusions no longer required them during treatment. The median overall survival rate was 15.5 months, which appeared to match the effectiveness of the traditional injection-based approach.

“Our study found, in an indirect comparison, similar efficacy in terms of survival and responses and safety data to the standard regimen,” says Zeidan. “The clinical data is best reflected in the lives of super responders.”

One such case is of 83-year-old Pamela Young, who has been in complete remission for almost three and a half years following the pill-based regimen. “I was attracted because it was two pills and it's been nothing but improvement,” she says.

This all-oral combination has now been approved by the FDA as a standard-of-care option for patients newly diagnosed with acute myeloid leukemia who are older or cannot undergo intensive chemotherapy, Zeidan says. He and his team plan to use these two pills as a standard treatment and in clinical trials as a backbone on which they can incorporate additional targeted oral drugs to hopefully further improve outcomes.

Zeidan is also leading a large study involving 1,300 patients globally with the goal of combining another innovative therapy called Ziftomenib with other standard therapies for patients with acute myeloid leukemia with the goal of improving their outcomes.

“We continue to emphasize our ability to deliver the best clinical care, top-notch research, and cutting-edge clinical trials, so that we can always offer our patients coming to Yale the best chance at fighting against leukemia,” says Zeidan.

For Young, this home-based pill treatment has not forced her to put her life on hold. “I’ve never been away from anything. I’ve been feeling great the whole time I’ve been treated,” she says. “It turned out to be a very positive thing.”