MRD assessed by WT1 and NPM1 transcript levels identifies distinct outcomes in AML patients and is influenced by
Juliette Lambert1, Jérôme Lambert2, Olivier Nibourel3
1Department of Hematology, Hôpital de Versailles, Le Chesnay, Université de Versailles-Saint Quentin; France.
Abstract:
We analysed the prognostic significance of minimal residual disease (MRD) level in adult patients with acute myeloid leukemia (AML) treated in the randomized gemtuzumab ozogamicin (GO) ALFA-0701 trial. Levels of WT1 and NPM1 gene transcripts were assessed using cDNA-based real-time quantitative PCR in 183 patients with WT1 overexpression and in 77 patients with NMP1 mutation (NPM1mut) at diagnosis. Positive WT1 MRD (defined as > 0.5% in the peripheral blood) after induction and at the end of treatment were both significantly associated with a higher risk of relapse and a shorter overall survival (OS). Positive NPM1mut MRD (defined as > 0.1% in the bone marrow) after induction and at the end of treatment also predicted a higher risk of relapse, but did not influence OS. Interestingly, the achievement of a negative NPM1mut MRD was significantly more frequent in patients treated in the GO arm compared to those treated in control arm (39 % versus 7% (p=0.006) after induction and 91% versus 61% (p=0.028) at the end of treatment). However, GO did not influence WT1 MRD levels. Our study supports the prognostic significance of MRD assessed by WT1 and NPM1mut transcript levels and show that NPM1 MRD is decreased by GO treatment.
Insights
Minimal residual disease (MRD) levels in acute myeloid leukemia (AML) impact relapse risk. Gemtuzumab ozogamicin (GO) treatment reduced NPM1 mutation MRD, but not WT1 MRD, suggesting a targeted therapeutic effect.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Minimal residual disease (MRD) is a critical prognostic factor in acute myeloid leukemia (AML).
- Assessing MRD using molecular markers like WT1 and NPM1 mutations provides valuable prognostic information.
- The role of targeted therapies in modulating MRD levels requires further investigation.
Purpose of the Study:
- To evaluate the prognostic significance of WT1 and NPM1 mutation minimal residual disease (MRD) in adult AML patients.
- To determine the impact of gemtuzumab ozogamicin (GO) treatment on MRD levels in AML.
- To correlate MRD levels with clinical outcomes such as relapse risk and overall survival.
Main Methods:
- Analysis of WT1 and NPM1 mutation transcript levels using real-time quantitative PCR in 183 and 77 adult AML patients, respectively.
- MRD assessment was performed after induction and at the end of treatment in the randomized ALFA-0701 trial.
- Statistical analysis to correlate MRD status with relapse and overall survival (OS) in patients treated with or without GO.
Main Results:
- Positive WT1 MRD after induction and end of treatment correlated with higher relapse risk and shorter OS.
- Positive NPM1 mutation MRD predicted higher relapse risk but did not affect OS.
- Negative NPM1 mutation MRD was achieved more frequently in the GO arm compared to the control arm (39% vs 7% post-induction; 91% vs 61% end of treatment).
- GO treatment did not significantly influence WT1 MRD levels.
Conclusions:
- WT1 and NPM1 mutation MRD levels are significant prognostic indicators in AML.
- NPM1 mutation MRD levels are favorably impacted by gemtuzumab ozogamicin treatment.
- MRD assessment provides crucial insights into AML prognosis and treatment response.
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