Precision Medicine Leading to New Options for AML Patients

Combination targeted therapies may be the next step for research.

In 2009, a patient with acute myeloid leukemia (AML) was the first person with cancer to have his or her whole genome sequenced, helping scientists to learn more about the molecular drivers of the disease. Despite the knowledge gained, researchers have struggled to develop therapies that specifically shut down those drivers.

But this year brings hope for patients with AML, with the approvals of several new treatment options, including therapies that target specific molecular mutations. Dr. Gwen Nichols, chief medical officer for the Leukemia & Lymphoma Society (LLS), believes that these targeted therapies are helping to usher in the era of precision medicine in AML. As we recognize Blood Cancer Awareness Month, Dr. Nichols explains the challenges of translating knowledge into treatments and why she is excited about the future of precision medicine in AML.

Dr. Gwen Nichols, chief medical officer for The LLS, is hopeful about the future of precision medicine in AML.

Dr. Gwen Nichols, chief medical officer for The LLS, is hopeful about the future of precision medicine in AML.

Why has treating AML remained a challenge?

“AML is a complex and dynamic disease that really needs a precision medicine approach to treat appropriate patients. Some patients diagnosed with AML will respond to standard chemotherapy regimens, but most will relapse. Chemotherapy targets highly proliferating cells but may be missing the cells that initiated the AML. Those cells remain behind, recover and can cause the disease to come back in AML patients. This is one reason why the five-year survival rate for AML patients remains low at just 27 percent.

Why has it been challenging to develop targeted therapies for AML?

“When the AML genome was sequenced, researchers thought they were going to find single mutations that drive the disease. They believed that if you got rid of this single molecular abnormality, you could get rid of the disease. We have found a few of these mutations in other cancers, such as in the Bcr-Abl tyrosine kinase in chronic myeloid leukemia. But over the last decade, we’ve learned that some cancers, including AML, are more complex and driven by multiple factors. So an effective therapy targeting one mutation won’t be the end of the story because it’s only one piece of the puzzle. As we work toward the future of precision medicine, we need to look at multiple targeted therapies in combination.”

 AML is a complex and dynamic disease that really needs a precision medicine approach to treat appropriate patients.


What type of diagnostics would you like to see to facilitate precision medicine in AML?

“In a perfect world where it costs nothing and can be done rapidly, you would sequence a patient’s genome as frequently and as completely as possible. The targeted sequencing that doctors are doing for AML patients today makes the most sense because that information can help determine diagnosis and prognosis. But I fear that we may be missing valuable information by not sequencing more of our patients’ genomes. We also need to sequence at intervals to make sure the disease has gone away and again when there’s evidence that the disease is coming back. We can’t assume that it’s the same [form of the] disease when it returns.”

How do the clinical trial designs need to change for precision medicine?

“In diseases such as AML, it’s clear that there are subsequent mutations as the disease progresses and that the disease becomes more complex as it evolves. Most therapies are first tested in patients with relapsed or refractory disease, but you cannot expect a targeted agent to be effective when other driving mutations have arisen. This is a recipe for failure. We may be throwing out therapies that could benefit patients because we are testing them at a time when the disease is so complex that there’s little hope for a single therapy to be effective. That’s why the LLS’ Beat AML Master Trial is focused on newly diagnosed AML patients.”

What needs to happen to truly enable precision medicine in AML?

“The last couple of months have been exciting with several new therapies introduced for AML. We are seeing real progress toward that now with this first wave of targeted therapies. With over 700 clinical trials active or recruiting in AML, there is certainly more to come. But the hope would be to have several different therapies available that target all the drivers of AML. These therapies will not be developed on their own. We need to think about the best way to help facilitate the future of precision medicine through novel trial design and combinations.”

For more information on the progress of precision medicine, read “Getting Patients Access to ‘Precision’ Medicine Is Crucial.”