Newly identified mutations in AML may help refine risk classification, optimize treatment
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The 2017 European LeukemiaNet recommendations should be refined to include certain gene mutations that could help determine which patients with acute myeloid leukemia require more intensive treatment, according to study results.
“My mentor, Clara D. Bloomfield, MD, was a member of the European LeukemiaNet, and strived to test its performance in different applications to potentially improve upon it. We had additionally clinically observed that not all patients classified as ‘favorable risk’ according to the recommendations had favorable outcomes,” Ann-Kathrin Eisfeld, MD, assistant professor in the division of hematology at The Ohio State University, told Healio. “In order to serve our patients better and provide more accurate information on what their prognosis may look like when treating them with standard chemotherapy, we decided to conduct this study, which is very close to my heart.”
Researchers dedicated the paper, published in Leukemia, to the memory of Bloomfield, who died during its completion.
The 2017 European LeukemiaNet recommendations (ELN 2017) have become a key tool to measure prognosis and guide treatment of patients with AML.
Eisfeld and colleagues sought to examine the molecular characteristics and outcomes of 863 patients with AML (median age, 45 years; range, 17-59; 55% men; 85% white) included in Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology studies who received treatment according to the ELN 2017 recommendations.
Nearly half (49%) of patients had been categorized as favorable risk, with 22% deemed intermediate risk and 29% classified as adverse risk. Patients in the adverse-risk group were more likely to be men (62% men vs. 38% women; P = .01), whereas the favorable- and intermediate-risk groups had similar proportions of men and women. Moreover, patients in the adverse-risk group were more likely to present with lower white blood cell counts (median, 20.710/L) than patients in the favorable-risk (median, 24.210/L) and intermediate-risk (median, 28.610/L) groups.
Researchers identified 2,354 mutations among all patients, including additional mutations to those that define ELN risk groups. They compared the frequencies of each mutation within the three risk groups to determine associations with better or worse outcomes and, thus, the potential of these mutations to refine the ELN 2017 risk-group classifications.
Results showed patients in the favorable-risk group with BCOR or SETBP1 mutations and noncore-binding-factor AML and patients in the adverse-risk group with IDH mutations had intermediate-risk outcomes. Outcomes of patients with NPM1/WT1 co-mutations and patients with ZRSR2 mutations mirrored those of patients in the adverse-risk group.
Further, patients with FLT3-ITD-high allelic ratio had adverse-risk outcomes instead of intermediate risk — regardless of NPM1 mutation status. DNMT3A mutations appeared associated with poor outcomes.
Based upon the refined classification data, researchers concluded that 4% of the ELN 2017 favorable-risk group and 9% of the adverse-risk group should be reclassified as intermediate risk. Additionally, 9% of the ELN 2017 favorable-risk group and 53% of the intermediate-risk group should be reclassified as adverse risk.
“We believe that with the identification of additional gene mutations that can refine risk groups of [patients with AML] that we will be able to identify which patients benefit from standard therapy, and also which patients have worse outcomes and might require additional consolidation treatment or a different therapy altogether,” Eisfeld said.
AML is an exciting field, with many promising new drugs having been approved or tested within clinical studies during the past few years, Eisfeld added.
“Future research should include patients treated with other treatments and regimens, such as hypomethylating agents or IDH inhibitors, to better assess what the optimal, personalized treatment for each patient with AML should be based on their genomic information,” Eisfeld said.
For more information:
Ann-Kathrin Eisfeld, MD, can be reached at The Ohio State University, 281 W Lane Ave., Columbus, OH 43210; email: ann-kathrin.eisfeld@osumc.edu.
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