Beat AML: Early Results Show Feasibility of Molecularly Driven Studies in AML

Early results from the Beat AML Master Trial confirmed the feasibility of a precision medicine treatment assignment in phase 1 and 2 clinical trials of newly diagnosed acute myeloid leukemia (AML).

According to the study, it is known that somatic genomic alterations contribute to the pathogenesis of AML, but the disease has seen few advances in the past 40 years. Currently, patients have few therapeutic options, particularly those who are aged 60 or older.

The Beat AML Master Trial aimed to advance therapy in this patient population by developing effective, personalized approaches based on genomics. 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.

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 substudies, 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 novel agent plus HMA if they have no response
• upfront combination of a novel agent plus HMA
• a novel agent plus intensive chemotherapy for select groups

At data cutoff, the study had enrolled 268 patients with a median age of 72; 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 7 days, and almost all patients were assigned to treatment by 7 days, meeting feasibility requirements. Ten patients had delayed treatment assignment, one due to suboptimal specimen quality and nine due to technical or instrumentation failure. All patients had cytogenetics available by 7 days.

Of the 210 patients enrolled, 23 patients went on an alternative trial deemed better for them than Beat AML and 40 patients received other standard-of-care therapy. Of those going onto treatment, 52.4% received treatment on one of the Beat AML substudies.

The researchers said the data confirm the feasibility of a rapid precision medicine approach to treating patients with newly diagnosed, previously untreated AML. They highlighted that the Beat AML trial is a unique model using genomic analysis to inform, accelerate, and improve drug development for blood cancers. Amy Burd, PhD, of the Leukemia and Lymphoma Society, presented results of the study at the 60th ASH Annual Meeting and Exposition.

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