Prognostic significance of deep sequencing for analysis of measurable residual disease in acute myeloid leukemia with NPM1 mutation.

In acute myeloid leukemia with NPM1 mutation, analysis of measurable residual disease (MRD) with reverse transcription quantitative polymerase chain reaction (RT-qPCR) is recommended for response assessment and monitoring after treatment. For rare mutations in NPM1, this is not readily available. Therefore, we evaluated the prognostic value of deep sequencing covering all NPM1 exon 11 variants, using retrospectively analyzed bone marrow samples from 97 patients in remission during treatment. MRD positivity was defined as NPM1 mutation at ≥0.05% variant allele frequency based on a previous comparison with RT-qPCR. Deep sequencing MRD positivity at any time during consolidation predicted relapse-free survival (at 3 years: 23.1 ± 11.7% vs. 70.8 ± 6.1%, p < 0.001) and overall survival (at 3 years: 30.8 ± 12.8% vs. 63.8 ± 6.6%, p = 0.014). In multivariable analysis, MRD status during consolidation was the sole predictor for relapse. In conclusion, deep sequencing of NPM1 has high prognostic value and extends MRD monitoring to patients with rare mutations in NPM1.