University of Colorado (CU) Cancer Center researchers have been on the leading edge of developing new therapies for leukemia. One of the most recent breakthrough therapies has been the development of venetoclax, a B-cell lymphoma-2 inhibitor, that that has shown profound results for adults with acute myeloid leukemia (AML) and has become a standard of care for patients with this disease all over the world.
On Friday, Dan Pollyea, MD, MS, a CU Cancer Center member and associate professor of medicine in the Division of Hematology at the CU School of Medicine, will present some of the most exciting breakthrough research in treating leukemia to the Colorado House Public & Behavioral Health & Human Services Committee.
“We’ve been really excited about telling this story and sharing what we’ve been able to accomplish here,” Pollyea says. “In the last couple of years, thanks to these efforts, Colorado is viewed as ground zero for venetoclax, and we’re really proud of that and proud to be associated with that.”
Developing a breakthrough therapy to treat leukemia
Historically, adults with AML have had “very poor outcomes and very limited treatment options,” Pollyea explains. “Starting in 2015, we helped to develop this new therapy that’s called venetoclax.”
One of the ways that venetoclax works is by stopping leukemia stem cells, the root cause of the disease and the source of relapse when it occurs, from using energy. Amazingly, it is able to do this without impacting normal stem cells from using energy.
CU Cancer Center researchers took a two-pronged approach to the venetoclax clinical trial, recruiting patients for the study while also studying the drug to understand how it works. Ultimately, they were able to prove it is the first cancer treatment that successfully attacks and destroys the stem cell population of cancer.
“Other treatments for leukemia are kind of indiscriminate,” Pollyea says. “They’re designed to kill the bulk population of the tumor, which is 99.9% of disease, but when you leave behind the roots, even if it’s a tiny fraction of the population of cancer cells, you will see the disease relapse.”
By attacking leukemia stem cells, venetoclax is able to eradicate those roots. Pollyea credits the nearly 100 University of Colorado participants in clinical trials for venetoclax for what researchers know about this drug and its 2018 Food and Drug Administration approval – an approval that happened with almost unheard-of swiftness because the treatment therapy was so effective.
“The patients from Colorado and the region who participated in the trials were pioneers,” Pollyea says. “They led the way and showed that this was an incredibly exciting treatment. We knew years before we even got FDA approval that this was going to change everything, and that’s thanks to courageous patients who agreed to receive an experimental therapy.”
A starting point for further leukemia research
In venetoclax trials, the vast majority of patients responded to the drug, many of whom achieved durable remissions. Venetoclax has now become the standard of care for AML in many situations for adults around the world.
These successes have led to further, ongoing research to understand the reasons why some adults with AML who take venetoclax don’t respond. “Why do some people relapse, and how can we make this therapy even better?” Pollyea says. “We’ve never really seen a therapy work like this before in the way that it attacks a particular metabolic weakness that stem cells have, and there is so much to learn.”
This research is a really exciting success story, Pollyea says. “We’re grateful for the opportunity to show how hard work and grant funding has led to breakthrough treatment that’s now standard of care, and thrilled that this has been able to attract some of the best and brightest colleagues from all over to want to come here and work with us. We’re proud that this could happen in Colorado.”
April 1, 2024