New oral regimen matches standard intravenous therapy for acute myeloid leukemia
· News-MedicalNearly half of patients (46.5%) achieved complete response, while 63% experienced either complete response or complete response with incomplete hematologic recovery, meaning cancer cells were undetectable, but the patient's healthy blood cell counts had not yet returned to normal. The median overall survival reached 15.5 months—comparable to existing intravenous therapies.
The combination of decitabine-cedazuridine and venetoclax received U.S. Food and Drug Administration approval on May 13 for the treatment of AML in newly diagnosed adults 75 years or older and patients clinically unable to undergo traditional, intensive chemotherapy. The study results were published June 3 in the New England Journal of Medicine.
Dr. Gail J. Roboz, lead author, professor of medicine and director of the Clinical and Translational Leukemia Program at Weill Cornell and oncologist, NewYork-Presbyterian/Weill Cornell Medical CenterHaving received approval, we anticipate that this oral AML regimen will become the standard of care for patients who are older or more frail. We hope these results point to a future for AML patients where the treatment journey is less disruptive and less burdensome without sacrificing outcomes."
Turning a standard into an oral treatment
AML is an aggressive blood cancer that can be diagnosed at any age and is especially difficult to treat in older adults and patients with other serious health conditions. For these individuals, the current standard treatment combines venetoclax with a class of drugs known as hypomethylating agents, such as decitabine. Venetoclax inhibits Bcl-2, a protein that leukemia cells overproduce to avoid cell death, while hypomethylating agents restore the activity of genes involved in cell growth and survival, helping slow leukemia progression.
However, this regimen requires monthly treatment cycles that combine oral venetoclax with five to seven days of an injectable hypomethylating agent delivered in a clinic or hospital. These frequent visits create significant physical, logistical and emotional challenges for patients and families.
More recently, pharmacologists developed a pill version of decitabine by pairing it with another drug called cedazuridine that prevents decitabine from being broken down when ingested.
The nonrandomized phase 1/phase 2 study enrolled 189 newly diagnosed AML patients at centers across the United States, Canada and Spain. The patients took a month of venetoclax, along with five days of decitabine-cedazuridine at the start of each treatment cycle.
The oral regimen demonstrated a safety profile consistent with what doctors already expect from standard AML therapies, which commonly deplete healthy blood cells alongside leukemia cells. The most common serious side effects included anemia (low red blood cell count), neutropenia (low numbers of infection-fighting white blood cells) and fever associated with low white blood cell numbers.
Tailoring treatment to reduce side effects
During the trial, researchers also investigated how to fine-tune the treatment schedule to optimize leukemia control, while minimizing side effects related to low blood counts.
The paper offers recommendations for physicians, including careful monitoring of leukemia cells until they reach a certain threshold and then strategically pausing venetoclax to allow the body to replenish normal white blood cells, red blood cells and platelets.
"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."
Looking ahead
For now, most patients taking the oral regimen must continue treatment to maintain remission, much like a chronic condition. "AML patients taking ongoing cycles of treatment require close monitoring but can still have an excellent quality of life," Dr. Roboz said.
In the future, the researchers hope that increasingly sensitive blood monitoring tests may identify when patients can safely stop treatment.
Dr. Roboz and AML researchers worldwide are also exploring "triplet therapies," which add additional targeted drugs to the decitabine-cedazuridine and venetoclax combination.
"The goal is to get away from treatment cycles that go on indefinitely," said Dr. Roboz. "We want to drive the leukemic cells to such low levels that patients can discontinue therapy and be cured."
This research was funded by Taiho Oncology, Inc., which manufactures INQOVI® (decitabine-cedazuridine).
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