There has been limited advancement in the treatment of acute myeloid leukemia over the past 40 years, with most patients undergoing intensive, toxic chemotherapy. Today, AML remains a deadly blood cancer, taking the lives of more than 10,000 patients each year, and less than 30 percent of patients live five years or longer after being diagnosed.
As the blood cancer community recognizes April 21 as the second annual AML Awareness Day, an innovative approach to clinical trials holds promise to overcome the research stagnation and explore tailored alternatives tailored for individual patients.
“A high unmet medical need exists for AML treatment,” Amy Burd, Ph.D., vice president of Research Strategy at The Leukemia & Lymphoma Society (LLS), said. The limitations of chemotherapy are especially notable for the elderly, she explained. “Older patients — those who are the most likely to be diagnosed with AML — cannot tolerate the standard chemotherapy regime. It’s just too toxic for them.”
One reason treatment remains challenging is that AML is not a single disease but a complex group of more than 10 different subtypes, some of which are more aggressive than others. And not all types respond to treatment equally.
In 2008, researchers sequenced the genome of AML tumor cells, improving the understanding of how the disease develops and, potentially, treatments it might respond to. With this knowledge in hand, scientists have developed targeted therapies that open up the possibility to tailor treatments for individual patients.
Last October, the LLS launched a unique clinical trial initiative called the Beat AML Master Trial, which matches patients with an investigational drug or drug combination potentially best suited to attack the specific mutations causing their cancer.
Their goal is to create nothing short of a paradigm shift in how AML is treated, moving away from the current one-size-fits-all approach.
But that shift requires a change in the clinical development culture — shaking up business as usual for clinical trials. A typical trial focuses on one or two therapies; but the Beat AML Master Trial is examining multiple treatments — including small molecule therapies, immunotherapies and checkpoint inhibitors — at multiple medical research centers across the country. The LLS has been coordinating the activities with the U.S. Food and Drug Administration, multiple biopharmaceutical companies, and at least 10 trial centers. LLS plans to enroll approximately 500 patients in this trial
“Putting all the pieces together is the biggest challenge with this initiative,” Burd said. “We have the DNA sequencing technologies, genomic analysis and targeted therapies. But how do we get to the point where they are working together in a way that is focused on what is best for each individual patient? This is a new approach for clinical trials and we think this Master Trial has the potential to stand as a model for future cancer clinical trials.”
Since the launch, they’ve already exceeded the targeted preliminary enrollment of 25 patients and provided those patients with personalized treatment plans. Enthusiasm among investigators and patients has been high, according to Burd.
“It speaks to the high unmet need in AML and desire for patients and doctors to have better treatment options,” Burd said. “Our mission has always been to put patients first. So we’ve incorporated patient-reported outcomes into the study to ensure they are getting the results that matter to them — whether that’s being able to walk around the block or run a marathon.”