Early Results of Beat AML Study Show Feasibility of Personalized Treatment Assignment

It is known that somatic genomic alterations contribute to the pathogenesis of acute myeloid leukemia (AML), but the disease has seen few advances in the past 40 years, and patients (particularly those 60 years old and older) have few therapeutic options. The Beat AML Master Trial aims to advance therapy in this patient population by developing effective, personalized approaches based on genomics. At the annual ASH meeting, study researchers presented data confirming the feasibility of a precision medicine treatment-assignment trial in patients with newly diagnosed AML.

From November 2016 through April 2018, the multicenter study enrolled patients age 60 years or older who had AML (non-acute promyelocytic with no central nervous system involvement), no prior therapy with a hypomethylating agent (HMA), and no clinical need for emergent therapy. The authors, led by Amy Burd, PhD, of the Leukemia and Lymphoma Society, and including researchers from Memorial Sloan Kettering Cancer Center, Ohio State University Comprehensive Cancer Center, and Oregon Health and Science University, said they aimed to determine the feasibility of a seven-day analysis and treatment assignment to a novel therapy.

Each patient who consented received a genomic screening upon diagnosis. A sample from a bone marrow biopsy was sent for a rapid analysis. The researchers then made treatment assignments using a prioritization schema that incorporated cytogenetics and somatic mutations present in a dominant AML clone with a variant allele frequency (VAF) > 0.3. If no cytogenetic abnormality or mutation with VAF ≥ 0.3 was observed, VAF ≥ 0.2 was used for treatment assignment.

Patients were assigned to receive personalized therapy on one of several sub-studies, each testing its own endpoints with one of the investigational therapies in one of the most prominent subsets of AML. The Beat AML study has 11 treatment arms that have been opened over time, and it involves seven novel agents. Patients receive one of the following:

  • a novel agent followed by a combination of the noel agent plus HMA if they have no response
  • a combination of a novel agent plus HMA at first
  • a novel agent plus intensive chemotherapy for select groups

At data cutoff, the study had enrolled 268 patients with a median age of 72 years (range 60 to 92); 43% were female. Of the 268 patients, 210 received treatment assignment (53 patients were ineligible, and five patients had a decision time pending at the time of the ASH abstract submission). All patients had cytogenetic results available by seven days, and almost all patients were assigned to treatment by seven days, meeting feasibility requirements. Ten patients had delayed treatment assignment, one due to suboptimal specimen quality and nine to technical or instrumentation failure.

The authors said the data confirm the feasibility of a rapid precision medicine approach to treating patients with newly diagnosed, previously untreated AML, also emphasizing that the Beat AML trial is a unique model using genomic analysis to inform, accelerate, and improve drug development for blood cancers.