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VIALE-A Trial Means New AML Treatments for Older Patients

VIALE-A Trial Means New AML Treatments for Older Patients
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Published on September 22, 2020

Another Promising New Treatment for Older Patients With AML

Older patients with acute myeloid leukemia (AML) have more effective treatment options than ever before but still face a poor prognosis: the relative survival for patients over age 75 is less than 3%, according to a study published in Cancer Medicine that used data from the U.S. Surveillance, Epidemiology, and End Results (SEER) program.1

And while the FDA has approved several drugs for use in patients age 75 and older with AML, including venetoclax (Venclexta) and glasdegib (Daurismo), these drugs are not curative.

“We have this, often, older patient population, where up until very recently we used lower intensity strategies, things like azacitidine (Vidaza), decitabine (Dacogen), low dose cytarabine (Cytosar-U),” said Dr. Courtney DiNardo in a recent Patient Power webinar. “They are effective for sure. But unfortunately, the majority of patients didn't respond well. It was not really seen as a durable curative treatment strategy.”

She added: “But all of that recently has changed.”

What is the VIALE-A Study for AML?

Dr. DiNardo, an associate professor of leukemia at the University of Texas MD Anderson Cancer Center in Houston, was the lead investigator for the Phase III VIALE-A trial, a study of patients age 75 and older who were newly diagnosed with AML or ineligible for intensive chemotherapy because of co-morbidities, such as heart disease or poorly controlled diabetes. The results of the study were published last month in the New England Journal of Medicine.  

In the trial, 431 patients (median age 76) were randomized in a 2:1 ratio to receive either the combination of venetoclax, a BLC-2 inhibitor, and chemo drug azacitidine or azacitidine plus placebo.

The addition of venetoclax to azacitidine improved remission rates to 66.4% compared to 28.3% with azacitidine alone and resulted in a median overall survival of 14.7 months compared to 9.6 months.

The responses to treatment were both rapid and durable: 43% of patients in the combination therapy group exhibited a response to treatment during the first cycle, and the observed median duration of remission was 17.5 months.

“The remission rates happen early after about one cycle only,” Dr. DiNardo said. “Which means that the majority of patients with leukemia who are going back and forth to the hospital, outside of the azacitidine injections, to get their lab counts checked, to get transfusions. This becomes a significant daily grind for patients with leukemia. It's a big burden. Patients going into remission, their counts normalize. So, that is no longer something where two to three times a week, they're traveling back and forth for counts and transfusions.”

New AML Therapy

Side Effects of AML Treatment

Dr. DiNardo said there are two main side effects associated with the combination regimen. The first is tumor lysis syndrome (TLS), “where we are doing such a good job at killing off the leukemia cells quickly that as those cells die, they can release chemicals into your bloodstream, and they can kind of start sludging in your kidneys and cause problems,” she explained.

However, in the clinical trial, when patients were managed proactively, no cases of severe TLS occurred, she said. “So, it's something to be aware of but is not a significant clinical concern if your physician is managing you for tumor lysis prevention appropriately.”

The second, she said, is neutropenia. A higher frequency of neutropenia (42% vs. 29%) and febrile neutropenia (42% vs.19%) was observed with the combination therapy compared to azacitidine and placebo. Neutropenia is an abnormally low count of neutrophils (a type of white blood cell) that increases the risk of infection.

“The therapy is so effective that by the end of the first month, the leukemia in the bone marrow is gone, but the counts haven’t fully recovered,” Dr. DiNardo said. “We often have to hold the venetoclax therapy for a week or two at the end of that first cycle, allow that normal bone marrow recovery to happen, allow counts to normalize... we want to make sure you're having that normal count recovery and really kind of not needing additional transfusions or having infections because you're counts are still suppressed.”

Improving Outcomes in Older AML Patients

The research findings are a potential game-changer for the treatment of AML in older patients, Dr. DiNardo said. While there have been new therapies, this is the first time in three or four decades that there has been a dramatic advancement in the outcome of older patients with AML, she said.

Still, while this combination regimen represents a key advance in AML therapy, many patients, unfortunately, will still relapse, Dr. DiNardo said. Future studies are needed to evaluate additional novel therapeutics in high-risk populations.

“…The role of the clinical researcher is to never say, ‘okay we're done. We've done as good as we're going to get and it's time for us all to go home,’” Dr. DiNardo said. “The point is to always be trying to improve upon that, whether it's improving tolerability or improving outcomes. So, this is definitely one of those important advancements.”

~Megan Trusdell

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1Incidence and survival of hematological cancers among adults ages ≥75 years.

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