Beat AML Trial Proves Feasibility of Rapid Treatment Assignment Following Diagnosis


Hematologists may have the ability to determine acute myeloid leukemia (AML) subtype based on genetic analysis of blood samples in 7 days or less, a process that could soon be an integral part of diagnosing and treating this patient population, according to Amy Burd, PhD.

Hematologists may have the ability to determine acute myeloid leukemia (AML) subtype based on genetic analysis of blood samples in 7 days or less, a process that could soon be an integral part of diagnosing and treating this patient population, according to Amy Burd, PhD.

Initial findings from the Beat AML study showed that rapid genetic testing in patients with AML was feasible and helpful, and that a precision medicine approach is possible for these patients, who must be treated urgently given the disease’s rapid progression.1

In the study, 273 patients aged 60 or older were identified as candidates for targeted therapy within 7 days of their samples arriving at a reference lab for testing, compared with just 12 who were not. “Implementation of a rapid treatment assignment umbrella study in elderly patients with AML is feasible, with [more than] 95% of patients assigned to treatment in less than 7 days,” Burd said during a press conference at the 2018 ASH Annual Meeting, where the data were presented.

The multiarm, multisite collaborative trial, led by the Leukemia and Lymphoma Society (LLS), is designed to test targeted therapy approaches for improving the generally poor prognosis among patients with AML.

“Acute myeloid leukemia is the most commonly diagnosed leukemia, with 20,000 patients a year and an overall survival of [approximately] 25%,” said Burd, vice president of research strategy at LLS, referring to the 5-year rate. “It is also the most lethal adult leukemia.”

“We know now that AML is a heterogenous disease. It is driven by the serial acquisition of mutations that lead to interpatient heterogeneity, in both biology and clinical response,” she added. “[Because of this], coupled with the increasing evidence of efficacy for targeted therapies in AML, we hypothesized: Could we improve outcomes by matching patients to the appropriate [targeted] therapy?”

In her presentation, Burd, lead study author of the Beat AML study, discussed whether a multicenter clinical trial could use genetic profiling to assign patients to molecularly defined, subtype-specific therapies within 7 days. In addition, the researchers aimed to delineate the potential for new therapies to improve outcomes among older patients with AML in the frontline setting.

Objectives of Umbrella Trial

The ongoing Beat AML trial has 3 primary objectives: to determine the feasibility of completing molecular, immunophenotypic, and/or biochemical studies in 7 or fewer calendar days; to assess the feasibility of assigning patients to substudies according to a master protocol, based on results from the testing; and to evaluate the clinical efficacy of novel treatment strategies in each of the substudies.

To be eligible, patients must be newly diagnosed with no prior ZAML treatment other than hydroxyurea and aged 60 years or older at the time of diagnosis. Burd noted these requirements are in line with FDA recommendations to incorporate broad eligibility criteria to capture the majority of patients with AML. The malignancy is most frequently diagnosed among people aged 65 to 74 years, with a median age at diagnosis of 68 years.2

Many of the patients enrolled were aged 75 years or older (n = 108; 37.9%) and male (58.6%). To create a genetic profile for each patient, the researchers applied 3 genetic analysis techniques: cytogenetics, polymerase chain reaction, and next-generation sequencing.

Patients were then considered for therapy using a precision medicine—based stratification algorithm that considered assignment for:

  • Known responsive attributes, such as core-binding factor (CBF) AML (CBF-AML) and NPM1 mutation-positive/FLT3 wild-type AML
  • Driver cytogenetic aberrations, such as 11q23/MLL-rearranged AML and TP53 wild-type/complex karyotype AML
  • A mutation clone with a variant allele frequency (VAF) ≥0.3 by next generation sequencing3

If patients were not assigned to a genomic group during initial stratification, A second run-through of the algorithm was performed assessing for a mutation clone with VAF ≥0.2.2

From highest to lowest, genomic stratification assignments were prioritized by CBF-AML, NPM1+/FLT3 wild-type, 11q23/MLL-rearranged, IDH2+, IDH1+, TP53+, TP53 wild-type/complex karyotype, FLT3-ITD+ or FLT3-TKD+, WT1+ or TET2+, and marker-negative AML.

Beat AML Update

The study, which launched on November 16, 2016, has enrolled 356 patients thus far; however, 66 patients were removed from the study because they turned out to not have AML upon laboratory analysis.

Of 285 patients who were identified as candidates for treatment, 146 have gone on to the second phase of the study, where they have been treated in a clinical trial for experimental therapies targeting their AML subtype.

Of those who have not been treated in phase II (n = 139; 48.8%), most chose other therapies such as standard care (n = 57; 20%), an alternative trial after assignment (n = 26; 9.1%), palliative care (n = 23; 8.1%), or an alternative treatment before clinical assignment (n = 20; 7%). Seven patients (2.5%) died during the 7-day period, and outcomes for 6 participants (2.1%) were considered “not specified” at the time of study analysis.

Burd emphasized that, although clinicians offered treatment assignment within 7 days, the ultimate decision was always guided by what was best for the patient, “even if that means a treatment [option] outside of the study,” she added.

In 2016, the study included just 3 experimental treatment arms; today, 11 substudies of therapies developed by 7 different pharmaceutical companies are ongoing under the Beat AML umbrella. These include studies into the novel drugs entospletinib, a SYK inhibitor; pevonedistat, an Nedd8 inhibitor; and BI 836858, an anti-CD33 monoclonal antibody. The study also has open arms testing 2 FDA-approved drugs: enasidenib (Idhifa), an IDH2 inhibitor, and gilteritinib (Xospata), a FLT3 inhibitor.

“The majority of patients assigned to protocol therapy proceeded to trial, with an increase in the frequency (of trial assignment) as new protocols opened,” Burd said. “And we’ve seen promising efficacy in several of the treatment arms to date.”

Because of AML’s rapid progression, and the urgency needed to start treatment as soon as possible, press conference moderator Joseph R. Mikhael, MD, chief medical officer of the International Myeloma Foundation, applauded the efforts of the Beat AML investigators: “One of the greatest challenges we’ve faced in the concept of precision medicine is that, by the time you determine what is best for that patient for diseases like AML and many other hematologic diseases, in a sense, the horse is already out of the barn, meaning you have to have started the patient on treatment already or else their disease could have progressed quite rapidly.”

“When we can employ the expertise of artificial intelligence, we can come up with those answers more quickly,” he added. “… trying to reduce that window within 7 days is important. To be able to obtain these results early is so fundamental.”


  • 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. Presented at: 2018 Annual Meeting; Dec. 1-4, 2018; San Diego. Abstract 559.
  • SEER Cancer Stat Facts: acute myeloid leukemia. National Cancer Institute website. Accessed December 2, 2018.
  • Mims AS, Kohlschmidt J, Borate U, et al. A precision medicine hierarchical classification developed using variant allele frequency (VAF) for treatment of older patients (pts) with acute myeloid leukemia (AML): Alliance Clinical Trials in Oncology (Alliance) historical patient control. Presented at: ASH Annual Meeting; Dec. 1-4, 2018; San Diego. Abstract 1489.

This article originally appeared on OncLive® as “Beat AML Trial Proves Feasibility of Rapid Treatment Assignment Following Diagnosis.”

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