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Post-Relapse Outcomes of Older Patients With NPM1-Mutated AML Are Favorable With Allo Transplant in Second Remission
Avraham Frisch1, Chezi Ganzel2, Yishai Ofran2
1Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, and Rappaport Faculty of Medicine-Technion, Haifa, Israel.
Abstract:
Molecular assessment of measurable residual disease (MRD) in NPM1-mutated AML patients is a powerful prognostic tool to identify the risk of relapse. There is limited data regarding MRD-guided decisions against alloSCT in elderly patients and FLT3-ITD co-mutation. We describe the outcome of NPM1-mutated AML patients in whom alloSCT was deferred based on ELN 2017 risk and MRD response. We report a relapse rate of 53% in this group, with a much higher incidence for older than 60 years patients than for younger patients (73% vs. 37%). When comparing outcomes of alloSCT in CR1 to intensive chemotherapy consolidation within each age group, patients over 60 years and patients with FLT3-ITD co-mutation had significantly lower RFS with intensive consolidation. Yet, in all subgroups, the lower RFS did not translate into OS difference, suggesting that relapsed NPM1 patients can often be salvaged and consequently achieve long-term remission. Our study supports the use of MRD response along with FLT3-ITD status in the decision to use post-remission therapy. We demonstrate that older patients and patients with FLT3-ITD-mutated AML have a high relapse rate but can be salvaged, leading to long-term survival.
Insights
Measurable residual disease (MRD) monitoring in NPM1-mutated AML aids relapse risk assessment. Older patients and those with FLT3-ITD mutations face higher relapse but can achieve long-term survival through salvage therapy.
Area of Science:
- Hematology
- Oncology
- Molecular Diagnostics
Background:
- Measurable residual disease (MRD) assessment in NPM1-mutated acute myeloid leukemia (AML) is crucial for predicting relapse risk.
- Limited data exists on allogeneic stem cell transplantation (alloSCT) decisions guided by MRD in elderly patients and those with FLT3-Internal Tandem Duplication (ITD) co-mutations.
Purpose of the Study:
- To evaluate outcomes of NPM1-mutated AML patients who deferred alloSCT based on European LeukemiaNet (ELN) 2017 risk stratification and MRD response.
- To analyze the impact of age and FLT3-ITD co-mutation on relapse-free survival (RFS) and overall survival (OS) after different post-remission therapies.
Main Methods:
- Retrospective analysis of NPM1-mutated AML patients.
- Assessment of MRD levels using molecular methods.
- Comparison of outcomes between alloSCT and intensive chemotherapy consolidation stratified by age and FLT3-ITD status.
Main Results:
- A 53% relapse rate was observed in patients who deferred alloSCT.
- Older patients (>60 years) had a significantly higher relapse rate (73%) compared to younger patients (37%).
- Patients over 60 and those with FLT3-ITD co-mutation showed lower RFS with intensive chemotherapy consolidation, but this did not impact OS, indicating successful salvage therapies.
Conclusions:
- MRD response, combined with FLT3-ITD status, is vital for guiding post-remission therapy decisions in NPM1-mutated AML.
- Elderly patients and those with FLT3-ITD mutations experience high relapse rates but can be effectively salvaged, achieving long-term survival.
