Morita K, et al. - Whether the degree of mutation clearance at remission predicts the risk of relapse in patients with acute myeloid leukemia (AML), was investigated. Clearance of somatic mutation at complete remission (CR), specifically in nonpreleukemic genes, was found to be related to significantly better survival and less risk of relapse. In AML, somatic mutations in nonpreleukemic genes may function as a molecular minimal residual disease marker.

Methods

• This study included 131 previously untreated patients with AML who received intensive induction chemotherapy and attained morphologic complete remission (CR) at day 30.
• Targeted capture DNA sequencing was used to analyze pretreatment and CR bone marrow.
• Based on the variant allele frequency (VAF) at CR, the link between mutation clearance (MC) was analyzed (MC2.5: if the VAF of residual mutations was < 2.5%; MC1.0: if the VAF was < 1%; and complete MC [CMC]: if no detectable residual mutations) and event-free survival, overall survival (OS), and cumulative incidence of relapse (CIR).

Results

• Data showed association of MC1.0 and CMC with significantly better OS (2-year OS: 75% v 61% in MC1.0 v non-MC1.0; P=.0465; 2-year OS: 77% v 60% in CMC v non-CMC; P=.0303) and lower CIR (2-year CIR: 26% v 46% in MC1.0 v non-MC 1.0; P=.0349; 2 year-CIR: 24% v 46% in CMC v non-CMC; P=.03), whereas no significant difference was found in any of the above outcomes by MC2.5.
• Significantly better event-free survival (hazard ratio [HR], 0.43; P=.0083), OS (HR, 0.47; P=.04), and CIR (HR, 0.27; P < .001) was observed in patients with CMC vs those without CMC in multivariable analysis adjusting for age, cytogenetic risk, allogeneic stem-cell transplantation, and flow cytometry–based minimal residual disease.
• Following removal of preleukemic mutations, such as DNMT3A, TET2, andASXL1, from the analysis, stronger prognostic associations were reported.