With a five-year survival rate of 27 percent, acute myeloid leukemia (AML), which starts in bone marrow and quickly moves into blood, is one of the most challenging cancers to treat in adults. There are several subtypes of AML and each responds differently to different therapies. That’s why a precision medicine approach, which customizes different treatments based on the uniqueness of one’s DNA, is more important than ever.
Recently, the FDA approved the first-ever drug to target a genetic mutation linked to AML. But now the hard work of showing the drug’s effectiveness in a large and broad population of patients has begun. With expertise in pharmaceutical and outcomes research, few people are better positioned to lead this charge than Masonic Scholar David Stenehjem, Pharm.D.
A specific drug for a specific gene
The novel drug that Stenehjem is studying, called midostaurin, targets an especially problematic subtype of AML called FLT3-mutated AML. One out of every three AML patients carry the FLT3 mutation, and those who have it relapse faster and die sooner than patients with other forms of AML.
Until recently, no drug has existed that targets mutations linked to AML, let alone FLT3.
Stenehjem believes that FLT3 inhibitors, like midostaurin, could make all the difference.
“FLT3 is a tyrosine kinase, which gives leukemia cells a signal to continue to grow, divide, and proliferate in an unrestrained manner,” explains Stenehjem. “Midostaurin works by inhibiting this tyrosine kinase and, ultimately, helps shut down the unrestrained proliferation of AML cells.”
Beyond clinical trials: drugs in the real world
But to be sure that midostaurin truly works, researchers must now show that it helps large populations of patients, and not just those selected for clinical trials.
“We know from the confines of clinical trials that midostaurin works well in a highly select group of patients who follow a pre-specified protocol,” Stenehjem says. “We are now working to determine the effectiveness of this drug in real-world populations.”
To achieve this goal, Stenehjem and his team have partnered with a major drug company to look at outcomes for large groups of patients with FLT3 mutations who take midostaurin versus those who do not.
First, they completed a baseline study of approximately 200 AML patients who had received standard AML therapies. Then Stenehjem’s team compared these patients to those who had taken midostaurin for FLT3-mutated AML. They found that patients treated with midostaurin achieved improved outcomes compared to patients who received standard therapies; however, more patients and time are needed before a definitive answer can be reached.
“The results demonstrate real-world evidence, in a limited data set, the benefit of adding midostaurin to traditional chemotherapy treatment for AML,” Stenehjem says. “Future research is warranted to assess long-term outcomes.”
After sharing their findings nationally and publishing their research, the next big step for Stenehjem and his team will be to secure significant grant funding for an expanded clinical study.
The power of big data
Stenehjem has worked on the scientific and clinical sides of pharmacy. He started his career conducting research in the lab of a pharmaceutical company and later launched a pharmacy practice of his own.
But as time went on, Stenehjem began to question the effectiveness of the drugs he prescribed and whether their benefits outweighed their costs and side effects.
“I was intrigued that many of our drugs were getting approved with very small margins of benefit,” he says. “This is especially true in oncology where we’ve seen approvals for drugs that provide as little as two weeks to two months of improvement in survival before the cancer returns. I wanted to examine whether these therapies are worth it.”
So Stenehjem’s path shifted into the rapidly growing field of outcomes research, which today is guiding his research on midostaurin in FLT3-mutated AML.
Outcomes research uses extensive patient data, typically from electronic medical records, that is pooled from different hospitals or institutions to determine the most effective and customized ways to detect, prevent, and treat different diseases.
“So much of this research is about quality data being collected by multiple institutions on a large scale,” explains Stenehjem. “Once we know the data points that are important to measure, it becomes essential to collect the data in a systematic and reproducible manner.”
Now, after plotting the key data points for studying AML therapies, Stenehjem’s team is working to roll them out to academic cancer centers nationwide that will uniformly capture outcomes for FLT3-mutated AML patients. This will increase the number of patients they are able to study from hundreds to thousands, lending validity and credibility to the study.
The impact of Masonic support
Over time, Masonic support has played a crucial role in propelling the early work of promising young scientists, enabling them to launch research that would not have otherwise been possible.
Stenehjem’s research is no exception. His group would not have been able to obtain pilot data on FLT3-mutated AML patients were it not for support from Minnesota Masonic Charities.
“Their giving enabled us to acquire preliminary data and to set up the infrastructure for these studies,” he says. “Without it, my time wouldn’t have been covered and we wouldn’t have been able to secure funding to complete the larger studies.”
“I want the Masons to how appreciative I am of their generosity. In the end, this work will lead to better outcomes for people with AML and an increased understanding of the effectiveness and value of a novel and promising therapy.”