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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.
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.
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
†n = 227
‡n = 227
§n = 91
‖n = 118
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)
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