Combination therapy is proving to be much more effective in treating acute myeloid leukemia (AML) than individual drugs, according to Dr. William Donnellan of Sarah Cannon Research Institute in Nashville, Tennessee.
“Unfortunately for AML, it's such a complicated disease,” said Dr. Donnellan, who is the director of Leukemia/Myelodysplastic Syndrome (MDS) Research. He spoke about AML treatments in a Patient Power webinar earlier this month.
“There are so many different genetic mutations that drive the disease,” he told Patient Power Co-Founder Andrew Schorr. “What we're learning is to target multiple pathways within an individual patient's leukemia, and then take multiple drugs and combine those. And what we're seeing is when we combine (these) drugs, they seem to work a lot better together than either one individually.”
Over the past three years, there has been an explosion of new drugs and an increasing pace of research in AML, Dr. Donnellan said. 2017 saw the approval of midostaurin (Rydapt) combined with chemotherapy to treat newly diagnosed adults with an FLT3 mutation, the most common mutation in AML. In 2018, the FDA approved venetoclax (Venclexta) in combination with azacytidine (Vidaza) or decitabine for AML in older patients.
“Now, previously, for patients diagnosed with AML, there weren't a whole lot of options,” Dr. Donnellan said. “You could give high-dose chemotherapy or not. And if patients were a little bit older, a little bit less healthy, there was a lot of risk of taking that high-dose chemotherapy. And so, what venetoclax has allowed us to do is to treat those older patients or patients who might have other health problems with a very effective combination.”
For example, when venetoclax is combined with azacitidine or decitabine, the remission rate is over 60 percent, he said. That’s compared to 10 to 15 percent when it is used as a single therapy.
Dr. Amer Zeidan, an associate professor of medicine (hematology) at Yale Cancer Center in New Haven, Connecticut, noted the explosion of AML treatments in an interview with Patient Power last month.
“For more than 45 years, the treatment for AML only involved intensive chemotherapy, and that was the only chance at a cure,” he said. “But since 2017, we’ve had a revolution in the treatment of AML after many years of no approved agents. I give an analogy in (terms) of ‘before Christ’ and ‘after Christ’ because the landscape has changed so much.”
The American Cancer Society estimates there will be 19,940 new AML cases this year. The average age at first diagnosis is 68. About half of patients who achieve remission after initial treatment will relapse.
Because AML is generally widespread throughout the bone marrow and possibly other organs, it is not staged like other cancers. The outlook depends instead on other information, such as the subtype of AML and the patient’s age. The five-year survival rate is about 25 percent, according to Cancer.Net. The prognosis is significantly worse for patients older than 60.
“So, we're talking about older adults,” Dr. Donnellan said. “In a lot of these newer medicines, these targeted therapies, they have very few side effects. They don't have the typical side effects of hair loss, nausea, vomiting that we think of when we think of chemo. In some cases, it's just a pill that patients take once a day, and they go about their way and do the things they enjoy doing.”
Still, Dr. Donnellan acknowledged that side effects are an issue – all cancer drugs have them. However, over the years, there has been a greater focus on side effect management.
“The other major advance in oncology over the last 10 or 20 years is supportive care,” he said. “Improving the anti-nausea medicines that are available, medications for pain, for anxiety. In a lot of clinics like mine, we integrate a supportive care team with the oncology team, with the end goal of helping people to live better lives.”
Watch the replay and read the transcript: AML Combined Therapies Are Changing Outcomes
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