Beat AML Trial Proves Feasibility of Rapid Treatment Assignment Following Diagnosis

Kristie L. Kahl
Published: Sunday, Dec 02, 2018

Amy Burd, PhD

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.

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