Oral leukemia therapy offers effective at-home care for older adults

For years, older patients with acute myeloid leukemia-an aggressive cancer of the blood and bone marrow-have needed clinic injections five to seven days a month, plus a daily oral pill. For these older patients, that clinic schedule can be quite demanding.

Now, a new all-oral therapy could let patients get treatment at home, saving them the trip to the clinic. A study published in the New England Journal of Medicine shows that the two-pill regimen works about as well as traditional injection-based treatments.

The regimen has now been approved by the United States Food and Drug Administration (FDA) for these patients 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. The main finding of our study is that we have replaced standard injection with a pill."

Amer Zeidan, MBBS, 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

Traditional chemotherapy comes with time toxicity

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 ran 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 replaced the traditional injection with two oral pills: a combination of decitabine (a chemotherapy that slows cancer growth and helps make healthy blood cells) and cedazuridine (an ingredient that lets decitabine work as a pill), plus venetoclax, an inhibitor that blocks a protein cancer cells need to survive.

Once a patient's bone marrow was clear of cancer, the team shortened how many days patients took the pills in later 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."

Pills are as effective as the current standard-of-care

In the trial, 47% of patients achieved a complete response-meaning no detectable signs of cancer remained-after the all-oral regimen. In addition, 63% of patients had a significant clinical response, and 60% of those who needed regular blood or platelet transfusions no longer needed them during treatment. The median overall survival was 15.5 months, matching 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 example is 83-year-old Pamela Young, who has been in complete remission for almost three and a half years after the pill-based treatment. "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 as a base in clinical trials for adding other targeted oral drugs to try to improve outcomes even more.

Zeidan is also leading a large global study of 1,300 patients that combines another new therapy, called Ziftomenib, with 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."