Distinct Patterns of Somatic Mutation Clearance and Association with Clinical Outcome in Patients with AML

Conference Correspondent - ASCO 2017 - Acute Myeloid Leukemia

Somatic mutations are associated with poor clinical outcomes in patients with acute myeloid leukemia (AML). However, there has been limited evaluation of the association between somatic mutation clearance (MC) and outcomes in patients achieving complete remission (CR).

A total of 95 patients with AML were treated with frontline induction and subsequently achieved CR. Pretreatment and CR bone marrow samples were sequenced, and the 3 levels of MC identified were MC2.5, persistent mutation with variable allele frequency <2.5%; MC1.0, persistent mutation with variable allele frequency <1%; and complete MC.

In the pretreatment samples, a total of 295 mutations in 78 genes were detected in 87 (92%) patients. In the matching CR samples, there were 131 mutations in 30 genes in 57 patients. In the ensuing analysis, mutations in transcription factors (MC2.5, 94%) or receptor tyrosine kinase (MC2.5, 88%) were found to have a high rate of MC. Conversely, mutations associated with clonal hematopoiesis of indeterminate potential (MC2.5, 33%), DNA methylation (MC2.5, 39%), and splicing pathways (MC2.5, 33%) showed a low rate of MC. Furthermore, patients who achieved MC1.0 or complete MC had significantly better relapse-free survival.

These findings suggest that somatic MC may help risk prediction of AML. In future studies of investigational therapies, MC rate in patients achieving CR may warrant consideration as an exploratory end point.

Takahashi K, et al. ASCO Abstract 7005.

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