Beat AML study paves way for precision treatment

Using genetic information to match patients to targeted therapies may improve survival in people with a fast-moving leukemia.

Because acute myeloid leukemia is such a fast-moving and deadly cancer, immediate treatment has been top priority in older adults. That has precluded the use of a precision approach to deeply analyze each patient’s cancer and select drugs that block specific vulnerabilities.

The Beat AML clinical trial has now shown that it’s not only feasible and safe to take time for DNA sequencing to target therapies, doing so also appears to improve outcomes. Patients who opted for the precision approach experienced a lower early death rate and superior overall survival compared with patients who opted for standard treatment, according to findings published in Nature Medicine.

Knight Cancer Institute Director Brian Druker, M.D., helped plan and develop the trial and OHSU was among the top four sites for enrolling subjects among 14 centers contributing. The study emerged from a collaboration started in 2013 by the Knight Cancer Institute and The Leukemia & Lymphoma Society.

AML is the most common acute blood cancer in adults — and one of the most difficult to treat. Each year, some 21,000 Americans are diagnosed with acute myeloid leukemia and 10,000 die from it. The five-year-survival rate for older adults is less than 20 percent, according to LLS.

The BEAT AML trial, which is ongoing at 16 cancer centers, is open to newly diagnosed patients age 60 and older. Researchers use a bone marrow biopsy to obtain tumor cells for next-generation sequencing. Results are used to assign participants to one of the trial’s sub-studies. (It opened in 2016 with three sub-studies but has since expanded to 11.)

The journal report describes results with 395 eligible study participants. Researchers were able to complete genetic and cytogenetic analysis within seven days for 374 subjects, nearly 95%. Of this group, 224 became Beat AML sub-study subjects with treatment based on genetic results, 103 chose standard-of-care treatment, 28 chose an investigational therapy, 40 chose palliative care, and 9 died before treatment assignment.

From the time of initial enrollment, 30-day mortality was about 4% for patients who joined a Beat AML sub-study, compared with 20% among patients who received standard-of-care treatment. “These prospectively obtained data support that, with notable exceptions, it is safe to delay treatment initiation for up to 7 days in elderly AML patients,” the authors said.

Overall survival estimates at 12 months were 55% in the Beat AML group, 28% in the standard of care group, 11% in the palliative care group, and 57% in the investigational therapy group. The authors point out that these data do not clearly differentiate the benefit of treatment assignment based upon a molecular target from better outcome that occurs simply from enrolling on a clinical trial; that determination will require studies with randomization of treatment assignment or comparison of targeted therapy to either real-world data or synthetic controls.

For a majority of patients it was possible to assign to a specific therapy based on molecular analysis of their cancer, and the ability to direct toward such a therapy increased as more sub-studies were added to the study. The proportion of patients without a targetable alteration decreased from 70% in 2016-2017 to 21% in 2018-2019.

Further reading:

Precision medicine treatment in acute myeloid leukemia using prospective genomic profiling: feasibility and preliminary efficacy of the Beat AML Master Trial by Amy Burd, Ross L. Levine, Brian Druker, John C. Byrd and others, Nature Medicine (Oct. 26, 2020)

Study in Nature Medicine shows superior patient outcomes in LLS’s Beat AML clinical trial, news release from The Leukemia & Lymphoma Society (Oct. 27, 2020)

The research was sponsored by LLS, which holds the investigational new drug (IND) application for the Beat AML clinical trial. The work was supported by donations from the Harry T. Mangurian Foundation and others, and by grants from the National Cancer Institute. Sub-studies were supported by the pharmaceutical sponsors.