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Abstract: E916

Type: Eposter Presentation

Background
The presence of minimal residual disease is known to be an independent prognostic factor for the duration of remission and survival in acute myeloid leukemia (AML). However, since AML has a molecular heterogeneity, the routine assessment of minimal residual disease (MRD) has not been adopted in the current practice of patients with AML.

Aims
 Herein, we evaluated the NPM1 mutation as a marker of MRD at first complete remission (CR) after induction therapy in normal karyotype AML (NK-AML) with favorable molecular risk group.

Methods
A total of 413 patients were included in the present study who met the following eligibility criteria: 1) age ≥ 15 years; 2) a diagnosis of NK-AML confirmed by conventional cytogenetic analysis; 3) treatment with induction chemotherapy using a standard protocol (a 3-day course of anthracycline with a 7-day course of cytosine arabinoside). Analysis of NPM1 mutations were performed using targeted resequencing by SureSelect capture and Illumina platform technology. The 184 patients (44.6%) showed NPM1 mutation at diagnosis and, 99 patients were NPM1 mutated and FLT3-ITD negative (favorable molecular risk by ELN). We have focused on the prognostic impact of NPM1 MRD esp. in the group with favorable risk by ELN risk classification. The 52 out of 99 favorable risk patients were available the analysis of NPM1 mutations at CR samples.

Results
In 52 patients, 37 patients (71.2%) were negative (NPM1^MRD-) and, 15 patients (28.8%) persistently observed the NPM1 mutations (NPM1^MRD+) in CR samples. There was no difference in variant allele frequencies of NPM1 mutations at diagnosis between NPM1^MRD- vs NPM1^MRD+ (32.7% [range, 6.85-43.9] vs 36.8% [range, 25.0-48.7], p=0.168). There was no difference in gender (p=0.754) or age (p=0.545). However, WBC count in NPM1^MRD- group (median: 15.3 x 10^9/L, range: 0.9-142.0) was lower than in the NPM1^MRD+ group (median: 81.1 x 10^9/L, range: 1.7-224.6.0), (p=0.014). In 15 out of 52 patients received allogeneic stem cell transplantation (SCT), there was no difference of proportion of patients receiving allotransplant between NPM1^MRD- vs NPM1^MRD+ group (21.7% vs.20.0%, p=0.897). In the survival analysis according to the MRD of NPM1 mutation, there was no difference between NPM1^MRD- vs NPM1^MRD+ group in terms of 5-year overall survival (OS) (NPM1^MRD- vs NPM1^MRD+, 66.1% vs.72.7%, p=0.699) and 5-year event free survival (EFS) (NPM1^MRD- vs NPM1^MRD+, 57.1% vs.61.1%, p=0.596). There was no difference in relapse risk at 5-year (NPM1^MRD- vs NPM1^MRD+, 36.4% vs.32.2%, p=0.509). Regardless of clearance of NPM1 mutations, allogeneic SCT substantially reduced the relapse risk (p=0.007). However, allogeneic SCT did not confer to overall survival benefit due to higher non-relapse mortality (p=0.046).

Conclusion
In this cohort, clearance of NPM1 mutation at first CR in favorable risk group of NK-AML was not replicated as a prognostic marker to predict the survivals or relapse risk. Even in patients with NPM1 positive at first CR in favorable molecular risk group, the most of patients demonstrated long term survival even with consolidation chemotherapy without allogeneic transplantation. To clarify the role of clearance of NPM1 mutations, further analysis after consolidative therapy will be needed.

Session topic: E-poster

Keyword(s): Acute myeloid leukemia, Minimal residual disease (MRD), Prognostic factor