Minimal Residual Disease and Risk Stratification in Acute Myeloid Leukemia
In an analysis of the UK National Cancer Research Institute AML17 trial reported in the Journal of Clinical Oncology, Freeman et al found that detection of measureable/minimal residual disease (MRD) after first induction in acute myeloid leukemia (AML) may be prognostically equivalent to partial response and may help identify NPM1 wild-type standard-risk patients who could benefit from allogeneic stem cell transplantation in first complete remission.
Study Details
As part of the AML17 trial, 2,450 younger adult patients (generally aged < 60 years) with AML or high-risk myelodysplastic syndrome underwent multiparameter flow cytometric MRD assessment after each induction course. After induction course 1, responses were categorized as resistant disease, partial remission, or complete remission/complete remission with incomplete blood count recovery, with the latter category assessed as MRD-positive or MRD-negative.
Patients without high-risk factors, including those with FLT3 internal tandem duplication wild-type and NPM1 wild-type disease, received a second daunorubicin/cytarabine induction, with course 2 being intensified for patients with high-risk factors.
MRD and Outcomes
Five-year overall survival was similar among patients with partial remission and MRD-positive responses after course 1, particularly among those with good to standard risk: 27% with resistant disease; 46% with partial remission; 51% with complete remission/complete remission with incomplete blood count recovery, MRD-positive; and 70% with complete remission/complete remission with incomplete blood count recovery, MRD-negative (overall P < .001). Adjusted analysis confirmed a significant difference in overall survival for resistant disease vs partial remission/MRD-positive response but not for partial remission vs MRD-positive (hazard ratio [HR] = 1.32, P = .4) among patients at good or standard risk.
A response of complete remission with incomplete blood count recovery after course 1 was associated with reduced overall survival vs complete remission in MRD-positive patients (19% vs 45%, P = .001), with a lesser effect observed after a second induction course. After adjustment for response during course 1, the prognostic effect of MRD-positive status after course 2 remained significant (hazard ratio [HR] for relapse = 1.88, P < .001; HR for survival = 1.77, P < .001), with MRD-positive status appearing to discriminate outcomes less among poor-risk patients.
Among NPM1 wild-type standard-risk patients, MRD-positive response in course 2 was associated with poorer 5-year overall survival vs MRD-negative response (33% vs 63%, P = .003). Although the number of involved patients was relatively small, analysis of the effect of stem cell transplant in first complete remission according to MRD status after induction course 2 suggested that a survival benefit might be more apparent with MRD-positive status (HR = 0.72, 95% confidence interval [CI] = 0.31–1.69) than with MRD-negative status (HR = 1.68, 95% CI = 0.75–3.85; P = .16 for interaction).
The investigators concluded, “[Multiparametric flow cytometry]-MRD can improve outcome stratification by extending the definition of partial response after first induction and may help predict NPM1 [wild-type] standard-risk patients with poor outcome who benefit from transplant in the first [complete response].”
The study was supported by Cancer Research UK and National Institutes of Health Research.
Sylvie D. Freeman, MD, PhD, of Birmingham Medical School, is the corresponding author for the Journal of Clinical Oncology article.
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