Persistent Leukemia-Associated Mutations After Induction Therapy Predict Poorer Outcome in AML
In a study reported in JAMA, Klco et al found that persistence of leukemia-associated mutations in ≥ 5% of bone marrow cells at remission predicted poorer outcome among patients with acute myeloid leukemia (AML), including those with intermediate-risk disease.
Study Details
In the study, whole-genome or -exome sequencing was performed in samples obtained at disease presentation from 71 patients with AML (mean age = 50.8 years) who received standard induction chemotherapy at Washington University School of Medicine starting in March 2002 and had follow-up through January 2015. Deep digital sequencing was performed in paired diagnosis and remission samples from 50 patients, including 32 with intermediate-risk AML, approximately 30 days after successful induction therapy; 25 were from the 71-patient cohort, and 25 were new cases.
Effect of Persistent Mutations
Analysis of comprehensive genomic data in the 71-patient cohort did not improve outcome discrimination compared with current risk-assessment methods. In the analysis of 50 patients with presentation and remission samples, 24 (48%) had persistent leukemia-associated mutations in ≥ 5% of bone marrow cells at remission, including 14 (44%) of 32 with intermediate-risk disease.
Median event-free survival was 6.0 months in those with persistent mutations vs 17.9 months in those with cleared mutations (hazard ratio [HR] = 3.67, 95% confidence interval [CI] = 1.93–7.11), including 8.8 vs 25.6 months (HR = 3.32, 95% CI = 1.44–7.67) in those with intermediate-risk disease. Median overall survival was 10.5 vs 42.2 months (HR = 2.86, 95% CI = 1.39–5.88), including 19.3 months vs 46.8 months (HR = 2.88, 95% CI = 1.11–7.45) in those with intermediate-risk disease.
The investigators concluded: “The detection of persistent leukemia-associated mutations in at least 5% of bone marrow cells in day 30 remission samples was associated with a significantly increased risk of relapse and reduced overall survival. These data suggest that this genomic approach may improve risk stratification for patients with AML.”
Timothy J. Ley, MD, of Washington University School of Medicine, is the corresponding author of the JAMA article.
The study was supported by grants from the National Institutes of Health, Barnes–Jewish Hospital Foundation, and National Cancer Institute. For full disclosures of the study authors, visit jama.jamanetwork.com.
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