FDA Approves New Combination of Drugs to Treat Acute Myeloid Leukemia

On October 16, the U.S. Food and Drug Administration (FDA) granted regular approval to venetoclax, a new drug, in combination with other standard treatments to treat patients with acute myeloid leukemia (AML). The FDA had initially granted the drug accelerated approval in November 2018. An August study published in The New England Journal of Medicine found that the therapy could reduce patient mortality by as much as 34%.

Venetoclax is to be used in combination with azacitidine, decitabine, or low-dose cytarabine (LDAC) for newly-diagnosed AML in adults 75 years or older, or those who have other conditions that don't allow them to undergo intensive chemotherapy.

“The prognosis in older patients with AML who are ineligible to receive intensive chemotherapy has been generally poor, and for decades there have been limited treatment options for these patients,” Tony Lin, PharmD, senior scientific director at AbbVie, the company that produces venetoclax, tells Verywell. “Our recent FDA approval is important because data from our VIALE-A trial has shown that Venclexta (venetoclax) plus azacitidine can help newly-diagnosed AML patients, who are ineligible for intensive chemotherapy, live longer than those treated with azacitidine alone.”

Improved Survival

The August study reviewed the effectiveness of two treatment options in 431 adults from ages 49 to 91 with AML. The candidates had not yet received chemotherapy for their diagnosis and were ineligible for aggressive chemotherapy treatment because of their age or coexisting medical conditions.

One group of 145 patients received azacitidine, an established drug of choice for AML in older patients who are not candidates for other chemotherapy drugs. The other 286 patients received azacitidine with venetoclax (Venclexta).

The patients treated with azacitidine alone had a median overall survival rate of 9.6 months. The patients who received azacitidine and venetoclax together had a median overall survival rate of 14.7 months.

Of those who took azacitidine and venetoclax together, 36.7% entered complete remission, compared to 17.9% of those who just took azacitidine alone.

Venetoclax and Azacitidine

In 2016, venetoclax was FDA-approved to treat chronic lymphocytic leukemia (CLL). Venetoclax is the first drug in a class of medications that binds to the B-cell lymphoma-2 (BCL-2) protein, which helps cancer cells survive. This prevents the protein from interacting with the cancerous cells, causing them to die off more quickly.

The FDA already approved venetoclax in combination with two other medications (decitabine or cytarabine) for AML patients 75 years or older who are not candidates for traditional chemotherapy.

Azacitidine is a type of chemotherapy drug known as demethylating agents. It targets cells with abnormal cancerous DNA. It is also thought to help bone marrow produce more normal red blood cells, reducing the need for blood transfusions.

“The standard chemotherapy is unfortunately not that effective,” Gwen Nichols, MD, chief medical officer for the Leukemia and Lymphoma Society, tells Verywell. “While the initial treatment can be effective, over 60 to 70% of adults relapse.”

Benefits of the Combination

One benefit of the combination of azacitidine and venetoclax is that it does not have to be given intravenously in a hospital. Venetoclax comes in a pill that can be taken by mouth. Many patients can receive azacitidine as an injection, similar to insulin.

Unlike with chemotherapy, patients do not need long-term IV access and there is a lower risk of complications related to IV site infections or malfunction.

“Patients don’t always have to stay in the hospital for this treatment," Nichols says. "Oftentimes they can get their medications at home or in the outpatient setting. From a quality-of-life view, it’s completely different.”

For individuals with AML who are not candidates for traditional aggressive chemotherapy, the new drug combination offers hope.

“It’s not a cure, but if you’re 75 years old and you get a couple more years of life, that’s a game-changer,” Nichols says. “Everything that moves us away from the traditional toxins is a step in the right direction.”

The treatment protocol is not yet well-established in children with AML, but Nichols says additional research is underway in younger populations. “The idea that venetoclax is a targeted agent is a hopeful one,” she says. “It doesn’t mean that we throw out chemotherapy because it’s still very effective, but the idea that we can do better is very exciting.”