Prognostic significance of deep sequencing for analysis of measurable residual disease in acute myeloid leukemia with <i>NPM1</i> mutation

In acute myeloid leukemia with <i>NPM1</i> 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 <i>NPM1</i>, this is not readily available. Therefore, we evaluated the prognostic value of deep sequencing covering all <i>NPM1</i> exon 11 variants, using retrospectively analyzed bone marrow samples from 97 patients in remission during treatment. MRD positivity was defined as <i>NPM1</i> 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%, <i>p</i> < 0.001) and overall survival (at 3 years: 30.8 ± 12.8% vs. 63.8 ± 6.6%, <i>p</i> = 0.014). In multivariable analysis, MRD status during consolidation was the sole predictor for relapse. In conclusion, deep sequencing of <i>NPM1</i> has high prognostic value and extends MRD monitoring to patients with rare mutations in <i>NPM1</i>.