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Impact of disease stage and MRD treatment on outcomes in patients with NPM1-mutated AML proceeding to allo-HSCT

May 28, 2024
Learning objective: After reading this article, learners will be able to cite a new clinical development in the treatment of acute myeloid leukemia.

NPM1 mutations in patients with acute myeloid leukemia (AML) indicate a favorable prognosis without allogeneic hematopoietic stem cell transplantation (allo-HSCT).1 Equally, patients with NPM1-mutated AML and positive measurable residual disease (MRD) often experience superior outcomes with allo-HSCT compared with chemotherapy.1 While MRD positivity prior to allo-HSCT is an adverse predictor of survival, the impact of disease stage at the time of transplant and of treatment for molecular positivity on patient outcomes remains unclear.1  

During the 50th Annual Meeting of the European Society for Blood and Marrow Transplantation, Bug presented results from a study investigating outcomes of patients with NPM1-mutated AML in relation to their disease stage at the time of allo-HSCT. We summarize the presentation below. 

Study design1 

  • A retrospective multicenter study 

  • Patient survival outcomes at the following disease stages were compared: 

    • Positive MRD in first complete remission (CR1) vs hematologic relapse 

    • Persistent MRD vs relapsed MRD 

    • Treated vs untreated molecular relapse 

  • Study endpoints were event-free survival, overall survival, cumulative incidence of relapse, and cumulative incidence of non-relapse mortality. 

Key findings1 

  • A total of 227 patients were enrolled in the trial 

    • Persistent MRD at CR1 (n = 46) 

    • Relapsed MRD at CR1 (n = 45) 

    • Primary refractory disease (n = 24) 

    • Hematologic relapse (n = 112) 

  • Survival outcomes for each patient subgroup are shown in Figure 1. 

Figure 1. Survival outcomes for A all patients after 4 years, B hematologic/molecular remission status, C persistent MRD vs relapsed MRD, and D positive MRD at CR1 vs CR2* 

CI NRM, cumulative incidence of non-relapse mortality; CIR, cumulative incidence of relapse; CR1, first complete remission; CR2, second complete remission; EFS, event-free survival; MRD, measurable residual disease; OS, overall survival. 
*Adapted from Bug.1 

  • Multivariable analysis showed the following factors to be associated with inferior overall survival: 
    • Untreated hematologic relapse (hazard ratio [HR] 3.91; p=0.009) 

    • Refractory relapse (HR 5.55; p<0.001) 

    • Primary refractory disease (HR 3.76; p=0.016) 

    • Unrelated human leukocyte antigen-mismatched donor (HR 2.13; p = 0.044) 

Key learnings 

  • Results from patients with persistent positive MRD and NPM1-mutant AML highlight the need for timely allo-HSCT to achieve negative MRD without additional treatment. 

  • Survival outcomes were equivalent for patients undergoing allo-HSCT with positive MRD at CR1 and patients with negative MRD. 

  • Survival outcomes were superior for patients who had positive MRD at CR1 vs those with hematologic relapse. 

  1. Gesine Bug. Excellent outcome of patients proceeding to allogeneic hematopoietic cell transplantation with untreated molecular relapse of NPM1-mutated AML. Oral abstract #OS1-07. 50th Annual Meeting of the European Society for Blood and Marrow. April 15, 2024; Glasgow, UK. 


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