Precision Medicine Approach Deemed Safe, Feasible for Older Patients With Untreated AML

A precision medicine treatment approach that incorporates genomic data into treatment decisions appears to be feasible in older patients with untreated acute myeloid leukemia (AML), according to a study published in Nature Medicine. Investigators also found that delaying treatment until mutational data were available did not seem to increase the risk of early death or adversely impact overall survival (OS).

According to the investigators of this study, delaying therapy to conduct detailed molecular profiling was considered safe, except for in patients with rapid proliferative disease or those with symptoms of leukostasis.

In this analysis of the ongoing Beat AML trial, researchers led by Amy Burd, PhD, of the Leukemia & Lymphoma Society (LLS), enrolled 487 patients aged 60 years and older with suspected AML. All consenting patients underwent bone marrow aspiration and biopsy, local pathology and cytogenetic analysis, next-generation sequencing, and FLT3-ITD ratio assessment to obtain cytogenetic and molecular findings.

Patients were then assigned to a specific treatment based on these results if they were turned around within 7 days. Clinicians were encouraged to maintain disease control with hydroxyurea during the treatment period.

A total of 395 patients in the trial were eligible to receive a treatment assignment based on their cytogenetic and molecular test results, but 374 patients had a completed genetic and cytogenetic analysis and were assigned a treatment within 7 days of sample receipt. The median age of the overall patient population was 72 years (range = 60-92). Approximately 38% of these patients were 75 years or older.

Most patients were assigned to LLS’s Beat AML sub-study (n=224). Patients in each of the Beat AML sub-studies were centrally assigned to a genetically defined therapy; those who did not meet the criteria for assignment based on genetic profiling were assigned to the marker-negative group or received alternative treatment.

In the group of patients who did not enroll in the assigned sub-study, treatment consisted of either standard of care chemotherapy (n=103), an investigational therapy outside of the Beat AML trial (n=28), or palliative/supportive care alone (n=40).

The researchers found that delaying treatment assignment for up to 7 days to conduct a molecular profiling analysis was safe.

Before treatment assignment, 9 patients died (2.3%), 32 began therapy before treatment assignment (8.1%), and 38 elected palliative care (9.6%). Adverse events of special interest, which included a decline in patient condition or AML progression prior to treatment initiation, occurred in 26 patients. The estimated 30-day mortality across all eligible patients was 14.1%, whereas the exclusion of patients who received palliative care generated an estimated 30-day mortality rate of 7.5%.

The first 2 patients who died during the study had MLL translocations and a rapidly rising white blood cell count that was required urgent treatment, the authors reported.

Over a median follow-up period of 7.1 months (range = 0-24.8), there were 194 deaths, for an estimated median OS of 10.0 months. Patients in the Beat AML group had a significantly longer median OS (12.8 months) compared with patients who received either standard chemotherapy (3.9 months) or supportive/palliative care alone (0.6 months). However, the rate of OS was not significantly different between Beat AML and the investigational therapy group (not reached).

The estimated 12-month OS rates according to treatment assignment were:

  • Beat AML: 54.7%
  • standard chemotherapy: 27.6%
  • supportive/palliative care: 11.0%
  • investigational therapy: 57.4%

Dr. Burd and colleagues wrote that, while the study demonstrated the feasibility of a precision medicine approach in older patients with AML, it did “not clearly differentiate the benefit of treatment assignment based on a molecular target from better outcome that occurs simply from enrolling on a clinical trial.”

To reach this determination, the study investigators suggest further research using “randomization of specific large genomic groups to targeted therapy versus standard of care or, in less common genomic groups, comparison of treatment with targeted therapy to either real-world data or synthetic controls.”

The study authors reported no conflicts of interest.


Burd A, Levine RL, Ruppert AS, et al. Precision medicine treatment in acute myeloid leukemia using prospective genomic profiling: feasibility and preliminary efficacy of the Beat AML Master Trial. Nat Med. 2020;26:1852-1858.