Rapid precision medicine approach feasible, improves OS among older patients with AML
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ORLANDO — The assignment of molecularly targeted therapies within 7 days of diagnosis appeared feasible and was associated with improved OS among older adults with acute myeloid leukemia, according to results of the Beat AML Master Trial presented at ASH Annual Meeting and Exposition.
Further, patients who participated in the Beat AML Master Trial — which is led by The Leukemia & Lymphoma Society — had a lower early mortality rate at 3.7%, compared with 20.4% among patients who elected standard of care, according to study results presented by Amy Burd, PhD, vice president of research strategy at Leukemia & Lymphoma Society.
“Our key finding showed we are able to deliver results in 7 days — and the 7-day time frame was not prohibitive — so that genomic information can be integrated into the management of these patients,” Jo-Anne Vergilio, MD, senior director of pathology and senior hematopathologist at Foundation Medicine, a key partner on the trial, told Healio. “Patients assigned to Beat AML treatment arms have shown improved OS and a reduction in early disease-related mortality.
“Looking at the genomics of AML, we appreciate that this disease is very complex,” she added. “The complexity emphasizes the importance of using genomic profiling early in the disease course to understand the biology. When we think about genomic profiling, there is always a focus on targeted therapy, which, of course, is important. But genomics can also be very important to upfront diagnosis, prognosis and management, even when a targeted treatment may not be identified. These are important nuances that are often undervalued in the hematology space.”
Burd and colleagues designed the Beat AML trial to assess the feasibility of using genetic profiling to assign patients to targeted therapies within 7 days of their initial diagnosis. Eligible patients were aged 60 years or older, had no known central nervous system manifestations, had not received hypomethylating agent therapy and were not in clinical need of immediate treatment.
“AML is one of the most common forms of acute leukemia in adults. If you look across all age groups, survival is 30%. However, it is worse in the older population,” Vergilio said. “We focused on AML in older patients because of that poor prognosis, and because although some therapies have arisen in the last few years, the standard of care has not changed in the last 40 years. This is clearly an area of great need.”
The trial included 395 patients (median age, 72 years; range, 60-92; 38% aged 75 years or older) — 16% of whom had treatment-related AML — who underwent profiling through local cytogenetic analysis and a central next-generation sequencing assay (Foundation Medicine), to acquire enough data to support treatment assignment within 7 days of diagnosis.
At the outset of this trial, there may have been skepticism in the clinical community that delaying treatment for 7 days could be done consistently and safely, Vergilio said.
“Because AML is so aggressive, patients are put on treatment within hours — it could be that same day or within 48 hours,” she said. “Clinicians do not wait 7 days to treat a patient. However, because treatment is initiated immediately, genomics are not available to guide that treatment. In order to bring a precision medicine trial to this particular group of patients with AML, we needed to wait the 7 days to enable processing of the samples and analysis of the findings.”
In total, 374 patients (94.7%) were centrally assigned within 7 days to different cytogenetic/genomic groups, the most common of which were TP53-mutated (19%) and marker-negative (18%) groups.
Of those with a treatment assignment, 224 consented to the Beat AML substudy. Of the other 171 patients, 103 received standard therapy (7+3 induction therapy or a hypomethylating agent), 28 received an alternative investigational agent, 38 received palliative care and two had an unknown treatment status.
Patients assigned a targeted therapy within the Beat AML substudy demonstrated significantly longer median OS than patients who received standard therapy (12.8 months; 95% CI, 10.3-14.8 vs. 3.9 months; 95% CI, 2.1-8.8; P < .0001).
Researchers estimated 30-day death rates of 3.7% (95% CI, 1.9-7.2) for those treated on the substudy, 20.4% (95% CI, 13-31.1) for those receiving standard therapy, 0% for those receiving an investigational therapy and 72.6% (95% CI, 57.8-85.7) for those receiving palliative care.
“Given the landmark nature of Beat AML, the hope is that this will be the paradigm for management overall,” Vergilio said. “If we can do this in a clinical trial, our goal should be to parlay and translate that to real-world practice so that all patients can be treated in a similar fashion.”
Beat AML has established a great model for using precision medicine approaches in different trial settings, she added.
“Globally, I would love to see broader precision-medicine based approaches in clinical trials within the arena of hematologic malignancies, and particularly for younger patients,” Vergilio said. “There certainly is an opportunity and a need to look at younger patients, because AML can affect anyone at any age.” – by Alexandra Todak
Reference:
Burd A, et al. Abstract 175. Presented at: ASH Annual Meeting and Exposition; Dec. 7-10, 2019; Orlando.
Disclosures: Burd reports no relevant financial disclosures. Vergilio reports equity ownership in Roche and employment with Foundation Medicine. Please see the abstract for all other authors’ relevant financial disclosures.