Precision medicine approach feasible, effective for AML
Click Here to Manage Email Alerts
Patients with acute myeloid leukemia who opted for biomarker-based treatment achieved better outcomes than those who opted for standard chemotherapy, according to results of the Beat AML Master Clinical Trial published in Nature Medicine.
Researchers also determined it is possible to identify potentially effective precision medicine approaches rapidly, meaning physicians and patients can incorporate genomic data into treatment decisions without increasing mortality risk.
“The study demonstrated that genomic analysis of the leukemia cells to identify AML subtypes can be completed safely within an unprecedented 7 days,” Amy Burd, PhD, vice president of research strategy for The Leukemia & Lymphoma Society, told Healio.
“The study shows that delaying treatment up to 7 days is feasible and safe, and that patients who opted for the precision medicine approach experienced a lower early death rate and superior OS compared with patients who opted for standard of care,” Burd added. “This is practice-changing because it gives doctors and patients critical information to guide more personalized treatment decision without risking the patient’s chance for survival.”
AML is the most common type of leukemia. Outcomes without allogeneic stem cell transplantation are poor, particularly among older patients.
Only 15% of patients aged 18 to 59 years and 2% of those aged 60 years or older remain disease free at 10 years, according to study background. Median survival among older patients treated with hypomethylating agents is 6.3 months.
AML treatment often begins within days of diagnosis, primarily due to the perceived risk for death due to disease progression. Consequently, even though deeper understanding of AML pathogenesis has contributed to the development of new therapies, a patient’s mutational profile typically is not factored into treatment decisions.
The Leukemia & Lymphoma Society designed the prospective Beat AML Master Trial to assess the feasibility of assigning treatment for older patients with AML based on molecular and cytogenetic results obtained within 7 days.
The trial launched in October 2016, and the Nature Medicine paper included data from 395 eligible patients aged 60 years or older (median age, 72 years; range, 60-92; 38% aged 75 years or older) with newly diagnosed AML. All but one patient underwent genetic and cytogenetic analysis within 7 days.
The majority (n = 224) enrolled on a Beat AML substudy; the other 171 opted for standard of care (n = 103), investigational therapy (n = 28) or palliative care (n = 40).
Burd and colleagues reported no significant differences in molecular, laboratory or demographic characteristics between patients who enrolled in a Beat AML study and those who opted to receive standard of care, which included induction with cytarabine plus daunorubicin or a hypomethylation agent.
The most commonly mutated genes among eligible patients included DNMT3A (28%), TP53 (26.5%), ASXL1 (23.4%), and TET2 (23.2%).
Researchers reported estimated 30-day mortality among all eligible patients of 14.1% (95% CI, 10.9-18.1). The rate was considerably lower among those who enrolled in a Beat AML substudy (3.7%; 95% CI, 1.9-7.2%) than those who elected for standard-of-care therapy (20.4%; 95% CI, 13.-31.2).
“These prospectively obtained data support that, with notable exceptions, it is safe to delay treatment initiation for up to 7 days [for elderly patients with AML],” researchers wrote.
Median follow-up for OS was 7.1 months (range, 0-24.8). During that time, 194 patients died.
Estimated median OS was 10 months (95% Ci, 7.8-12). Patients who enrolled in a Beat AML substudy achieved significantly longer median OS (12.8 months; 95% CI, 10.3-14.8) than those who chose standard-of-care therapy (3.9 months; 95% Ci, 2.1-8.8) or palliative care (0.6 months; 95% CI, 0.4-0.8), but not those who chose investigational therapy (median, not reached).
Estimated 12-month OS rates were 54.7% for those who enrolled in a Beat AML substudy, 27.6% for those who chose standard-of-care therapy, 11% for those who chose palliative care and 57.4% for those who chose investigational therapy.
The trial provides evidence that front-line treatment based on genomic-defined AML subtypes is feasible and safe for most patients, researchers concluded.
“Until recently, this type of analysis simply wasn’t available or could take months, causing risky delays in treatment,” Burd told Healio. “The study demonstrates a paradigm shift in how patients diagnosed with AML should be treated, proving that using genetic information to match patients to targeted therapies leads to better survival rates than the traditional one-size-fits all treatment approach.”
The Beat AML trial will continue to adapt to changes in the AML treatment landscape. The trial also “stands as a model for other cancer trials,” Burd said.
The Leukemia & Lymphoma Society recently launched Beat COVID — a trial that uses the Beat AML infrastructure — to evaluate the Bruton tyrosine kinase inhibitor acalabrutinib (Calquence, AstraZeneca) for patients with blood cancer who tested positive for COVID-19. The society also intends to launch the Stop MDS trial for patients with myelodysplastic syndrome and the LLS PedAL trial for children with acute leukemia.
Collapse
Read more about
Click Here to Manage Email Alerts