BEAT AML Umbrella Trial: Bringing Personalized Medicine to Acute Myeloid Leukemia

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THE MULTIARM, multicollaborative BEAT AML umbrella trial demonstrated the feasibility of using next-generation sequencing to assign treatment tailored to individual genomics of elderly patients with acute myeloid leukemia (AML) within 7 days. This may prove to be a major advance, since typically the wait for next-generation sequencing results is up to 1 month, and by that time, the disease can rapidly progress.

The rapidity with which next-generation sequencing results were obtained was the fruit of a collaboration between Foundation Medicine and The Leukemia & Lymphoma Society, which is sponsoring the BEAT AML trial.

Amy Burd, PhD

Amy Burd, PhD

“We have been able to do 7-day turnaround because we have a commitment from Foundation Medicine to prioritize our samples to generate results within the time frame we require,” explained lead author Amy Burd, PhD, of The Leukemia & Lymphoma Society. “The speed up of results was due to a prioritization of logistical flow for patients in the study, not with the actual process of genomic analysis.” Dr. Burd presented these results at the 2018 American Society of Hematology (ASH) Annual Meeting & Exposition.1

“Traditionally, the time it takes to get genomic analysis makes physicians reluctant to personalize therapy for each patient, and they often go to the traditional approach. Our approach comes up within a week to help tailor therapy for patients with AML, and it has already had an impact,” she said. “Early death and disease progression prior to treatment assignment are uncommon outside of mixed leukemia lineage–rearranged acute leukemias. The majority of patients assigned to protocol therapy proceeded to trial with increasing frequency as new protocols open. Promising efficacy is observed to date in several of the treatment arms,” she continued.

John C. Byrd, MD

John C. Byrd, MD

Senior author of this trial, John C. Byrd, MD, Distinguished University Professor and D. Warren Brown Chair of Leukemia Research, The James Comprehensive Cancer Center at The Ohio State University, Columbus, said: “The BEAT AML umbrella study is important for patients with AML. For the first time, this study moves treatment to an individual basis instead of treating newly diagnosed AML as a single entity. We are moving away from chemotherapy for patients where chemotherapy won’t cure the disease. Targeted therapy is more patient-friendly than what we have been using to treat patients.”

AML is the most commonly diagnosed and lethal adult leukemia, and the disease is highly heterogeneous. As more is learned about the genomics of the disease and more targeted therapies become available, it is likely that disease outcomes will be improved by matching patients to the right therapy, Dr. Byrd continued.

Study Description

THE BEAT AML TRIAL enrolled the first patients in November 2016. At the time of the 2018 ASH Annual Meeting, the study had enrolled 352 patients with newly diagnosed AML. Enrollment criteria included age of 60 years or older at the time of diagnosis; previously untreated AML with no prior treatment other than hydroxyurea; prior therapy for myelodysplastic syndrome, myeloproliferative disorder, or aplastic anemia is permitted but not with hypomethylating agents; and the ability to provide informed consent. “These broad eligibility criteria capture the majority of patients with AML,” Dr. Burd said.

“For the first time, this study moves treatment to an individual basis instead of treating newly diagnosed AML as a single entity.”
— John C. Byrd, MD

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Once next-generation sequencing results are received, patients are assigned to therapy according to the best option for curability based on dominant clones of any of the following abnormalities: core binding factor, NPM1 mutation/FLT3 wild-type; MLL rearrangements; IDH2 mutations; IDH1 mutations; TP53 mutations; complex karyotype with no TP53 mutations; FLT3 mutations; TET2/WT1 mutations (hypermethylation phenotype); and marker-negative AML. Of the first 285 patients enrolled in the BEAT AML trial, the median age was 72 years (range, 60–92 years), 37.9% were aged 75 or older, and 58.6% were male.

To begin, the researchers tested the feasibility of assigning patients to a targeted therapy within 7 days of samples arriving at the reference laboratory. Sixty-six patients were identified as having a diagnosis other than AML, 273 were assigned to therapy within 7 days, and 12 were not (thus, 95.8% were assigned within 7 days). “The answer to the feasibility question is ‘Yes,’” stated Dr. Burd.


  • The BEAT AML Trial illustrates the feasibility of using next-generation sequencing to assign treatment tailored to individual genomics of elderly patients with AML within 7 days of diagnosis.
  • This chemotherapy-free approach may improve outcomes.
  • Initial results from 2 of 10 ongoing trials are showing a therapeutic benefit.

Of the 285 patients assigned to treatment, 146 were actually treated based on the genomic abnormalities listed previously. Sixty-one patients were marker-negative. Of the 139 who were not treated according to the findings of next-generation sequencing, most chose other therapies, including the standard of care (20%), palliative care (8.1%), and alternative treatment (16.1%).

When the BEAT AML trial first started, there were 3 substudies according to treatment options, but over time, that number has increased to 11 substudies. One substudy that assigned patients with core binding factor to samalizumab induction has since been closed by the manufacturer, and that was “disappointing,” Dr. Burd said. The other 10 substudies are active at 13 clinical sites.

Dr. Burd updated attendees at an ASH press conference on the current results. A phase I dose-escalation study with BI 836858 plus azacitidine in patients with TET2/WT1 and marker-negative disease has completed phase Ib; the phase II recommended dose was 80 mg. An expanded phase II study of enasidenib plus azacitidine in 27 patients with IDH2 mutations yielded a 44.4% objective response rate.

“In the future, we are looking to expand our substudies into novel combinations. Thus far, the majority of patients enrolled are obtaining therapeutic benefit,” Dr. Burd said.

DISCLOSURE: Dr. Burd reported no conflicts of interest. Dr. Byrd has received honoraria from Acerta and Verastem, as well as research funding from Pharmacyclics and Jazz.


1. Burd A, Levine RL, Shoben A, et al: Initial report of the BEAT AML Umbrella study for previously untreated AML: Evidence of feasibility and early success in molecularly driven phase 1 and 2 studies. 2018 ASH Annual Meeting & Exposition. Abstract 559. Presented December 3, 2018.

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