Beat AML Master Clinical Trial Shows Promise for Precision Medicine in the Treatment of AML

Patients who participated in the Beat AML Master clinical trial were found to have superior outcomes with precision medicine, compared to patients with acute myeloid leukemia (AML) who opted for standard chemotherapy treatment, according to a study published in Nature Medicine.¹

Overall, the study demonstrated that a precision medicine therapy strategy in AML is feasible within 7 days of sample receipt and before treatment selection, allowing patients and physicians to rapidly incorporate genomic data into treatment decisions without increasing early death or adversely impacting overall survival (OS).

“The study shows that delaying treatment up to seven days is feasible and safe, and that patients who opted for the precision medicine approach experienced a lower early death rate and superior overall survival compared to patients who opted for standard of care,” corresponding author John C. Byrd, MD, D. Warren Brown Chair of Leukemia Research of The Ohio State University, said in a press release.² “This patient-centric study shows that we can move away from chemotherapy treatment for patients who won’t respond or can’t withstand the harsh effects of the same chemotherapies we’ve been using for 40 years and match them with a treatment better suited for their individual case.”

In the ongoing Beat AML trial, researchers prospectively enrolled untreated patients with AML who were 60 years or older with the aims of providing cytogenetic and mutational data within 7 days of the sample receipt and before treatment selection, followed by treatment assignment to a sub-study based on the dominant clone. In total, 487 patients with suspected AML were enrolled in the study and 395 were deemed eligible for analysis.

The median age of the participants was 72 years (range 60-92 years). Overall, 374 patients (94.7%) had genetic and cytogenetic analysis completed within 7 days and were centrally assigned to a Beat AML sub-study, while 224 (56.7%) were enrolled on a Beat AML sub-study. The remaining 171 patients elected to receive either standard of care (n = 103), investigational therapy (n = 28), or palliative care (n = 40). Moreover, 9 patients died before treatment assignment.

Demographic, laboratory, and molecular characteristics were not found to be significantly different between patients on the Beat AML sub-studies and those receiving standard of care (induction with cytarabine + daunorubicin [7 + 3 or equivalent] or hypomethylation agent).

However, 30-day mortality was less frequent, and OS was significantly longer for patients enrolled on the Beat AML sub-studies versus those who elected to receive standard of care. The median OS for patients included in the Beat AML trial was 12.8 months versus 3.9 months for patients opting for standard of care.

To date, the trial has now screened more than 1000 patients at 16 cancer centers. The data presented herein represents patient enrollment during a slice of time between November 17, 2016 and January 30, 2018.

“The study is changing significantly the way we look at treating patients with AML, showing that precision medicine, giving the right treatment to the right patient at the right time, can improve short and long-term outcomes for patients with this deadly blood cancer,” Louis J. DeGennaro, PhD, president and CEO of the Leukemia & Lymphoma Society (LLS), the conductor of the trial, said in the release. “Further, Beat AML has proven to be a viable model for other cancer clinical trials to emulate.”

Recently, LLS launched its Beat COVID trial, which leveraged the Beat AML infrastructure to quickly pivot to treat patients with blood cancer who are infected with the coronavirus disease 2019 (COVID-19) virus. The trial is testing the drug acalabrutinib (Calquence), which is currently approved to treat several types of blood cancers. The trial is open to patients diagnosed with all types of blood cancers.

Additionally, LLS is also planning other precision medicine trials modeled after Beat AML, including LLS PedAL, a global precision medicine trial for children with relapsed acute leukemia, currently on track to launch in summer 2021, and Stop MDS, a master trial for patients with myelodysplastic syndromes.

References:

1. STUDY IN NATURE MEDICINE SHOWS SUPERIOR OUTCOMES FOR PATIENTS IN LLS'S PARADIGM-SHIFTING BEAT AML CLINICAL TRIAL [news release]. Rye Brook, NY. Published October 26, 2020. Accessed October 28, 2020. https://www.lls.org/news/study-in-nature-medicine-shows-superior-outcomes-for-patients-in-llss-paradigm-shifting-beat-aml-clinical-trial?src1=182886&src2=

2. 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. Nature Medicine. doi: 10.1038/s41591-020-1089-8