In the Beat AML Master Trial, researchers are genomically sequencing patients newly diagnosed with acute myeloid leukemia, and using the results to assign therapies. The approach, which has identified several promising treatments, demonstrates how personalized medicine can be applied in a clinical setting.

Clinicians may be closer to applying personalized medicine to the treatment of acute myeloid leukemia (AML), according to findings from the ongoing Beat AML Master Trial. In this study, newly diagnosed patients are genomically sequenced, and the results are used to quickly assign first-line therapies.

Preliminary results were presented by Amy Burd, PhD, of the Leukemia & Lymphoma Society, during the 2018 American Society of Hematology Annual Meeting in San Diego, CA, in December. Burd noted that AML is not only one of the most common and most lethal adult leukemias, with an overall survival rate of 25%, but also highly heterogeneous, with numerous distinct genetic subtypes driven by different combinations of mutations. Increasing evidence that this disease may respond to targeted therapies prompted the question, “Could we improve outcomes by matching patients to the appropriate therapies?”

To find out, Burd and colleagues launched Beat AML, a large umbrella trial, in 2016. “The guiding principle is to move quickly and use the best science available, to try to identify patients where we'll see significant effects,” explained study co-leader Brian Druker, MD, director of the Knight Cancer Institute at Oregon Health & Science University in Portland. “The goal is to sequence the patient's leukemia, turn that around within 7 days, and then assign the treatment based on the genomics,” via an algorithm developed within the trial.

Burd highlighted the first 285 patients enrolled in the trial, all of whom were at least 60 years old and not previously treated for AML. Of these, 273 patients were assigned to therapies within 7 days, with 146 then going on to be treated in one of 11 study arms; the remaining patients either declined treatment or were assigned to therapies outside this study. She noted that Beat AML's commitment from Cambridge, MA–based Foundation Medicine to prioritize sequencing tumor samples from this trial is one factor contributing to the quick turnaround time.

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At the ASH meeting, Amy Burd, PhD, reported that sequencing and the assignment of patients to one of several treatment arms of the Beat AML Master Trial could be completed within a week.

Preliminary data from two Beat AML study arms were presented: According to a phase II trial, the IDH2 inhibitor enasidenib (Idhifa; Celgene), which is FDA-approved for patients with relapsed/refractory IDH2-mutant AML, is also active as a first-line therapy, eliciting an overall response rate of 44.4%. Meanwhile, a phase Ib trial established safety and dosing for the investigational anti-CD33 therapy BI 836858 (Boehringer Ingelheim) combined with azacitidine for patients with a DNA hypermethylation signature, and those without any mutations in leukemia-associated genes. This combination is now being tested in a phase II trial.

“The advantage of this [approach] is that you're really tailoring therapies to individual patients” based on the genomic landscape of their tumors, which is especially important as more targeted therapies become available, said Monica Guzman, PhD, of Weill Cornell Medicine in New York, NY, who is not involved in the research. “I think it's a great example of what personalized medicine should look like.”

Joseph Mikhael, MD, of the International Myeloma Foundation, who is also not connected to the trial, noted that it addresses one of the biggest challenges of implementing personalized medicine in aggressive diseases like AML: how long it often takes to perform genomic sequencing and analyze results. “To be able to obtain [genomic data] early is so fundamental,” he said, adding that the Beat AML Trial demonstrates how “we can come up with those answers more quickly.” –Catherine Caruso

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©2019 American Association for Cancer Research.
2019
American Association for Cancer Research.