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A promisingdrug combinationcould help people with leukemia who don’t respond to traditional treatments, according to new research.
A team at Oregon Health and Science University made the discovery by analyzing samples from more than 300 patients withacute myeloid leukemia, or AML.
More than 20,000 Americans are diagnosed with AML each year, making it one of the most common types of leukemia, data show.It is also one of the most aggressive.
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The researchers paired venetoclax, a drug commonly used to treat leukemia, with palbociclib, which is used forbreast cancer.This resulted in significantly stronger and more durable leukemia-fighting activity than venetoclax alone.
The findings were confirmed in human tissue samples and in mouse models carrying human leukemia cells.
Venetoclax, a drug commonly used to treat leukemia, paired with palbociclib, a cell-cycle inhibitor used in breast cancer treatment, resulted in stronger leukemia-fighting activity than venetoclax alone.(iStock)
“The data show that this drug regimen may be especially effective in patients whose tumors exhibit features that cause resistance to the current standard of care,frontline therapies,” Jeffrey Tyner, professor of cell, developmental and cancer biology in the Oregon Health &Science University�
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Tyner, who is part of the research team, noted that initial testing explored a broad range of drug combinations and did not begin with any specific “favorites.”
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Among all the pairings tested, including current standard-of-care regimens, the leukemia and breast cancer drug combination showed the most promising results.
“That really motivated us todig deeperinto why it works so well — and why it appears to overcome resistance seen with current therapy,” Melissa Stewart, research assistant professor at OHSU and lead author of the study, said in a press release.
More than 20,000 Americans are diagnosed with AML each year, making it one of the most common types of leukemia.(iStock)
The study found that AML cells exposed to only venetoclax were able to adapt by increasing protein production.Adding palbociclib, however, blocked this adaptation and impeded the cancer cells’ ability to survive.
“In this model, venetoclax alone didn’t extend survival at all — just as we’d expect based onthe genetics,” Stewart said.“But with the combination, the majority of mice lived 11 to 12 months.In fact, one mouse was still alive when the study ended.”
“Unfortunately, almost everyone will eventually have drug resistance.”
The study helps explain the biological reasons behind the better outcomes of this new drug combination, according to Tyner, and sets the stage for clinical trials withreal patients.
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The drug, which was approved by the Food and Drug Administration in 2019, is often combined with azacitidine, a different cancer medication.Resistance to treatment, even with this duo, remained nearly universal.
“Unfortunately, almost everyone will eventually have drug resistance,” Tyner said in the press release.
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“This regimen has improved initial response rates and quality of life, but the five-year survival rate for AML is still only about 25% to 40%.We have a lot of work to do,” he added.
The team says it does not yet have data for clinical activity in AML patients, other than some reported anecdotal cases.(iStock)
While the data strongly suggest that this new drug should be tested in clinical trials, the team says it does not yet have data for clinical activity in AML patients, other than some reported anecdotal cases.
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“So, the biggest limitation is also our desired next step — of testing this new drug combination in clinical trials,” Tyner said.
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