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Measurable residual disease at induction redefines partial response in acute myeloid leukemia and stratifies outcomes in patients at standard risk without NPM1 mutations

Freeman, Sylvie D., Hills, Robert K., Virgo, Paul, Khan, Naeem, Couzens, Steve, Dillon, Richard, Gilkes, Amanda, Upton, Laura, Nielsen, Ove Juul, Cavenagh, James D., Jones, Gail, Khwaja, Asim, Cahalin, Paul, Thomas, Ian, Grimwade, Davied, Burnett, Alan K. and Russell, Nigel H. 2018. Measurable residual disease at induction redefines partial response in acute myeloid leukemia and stratifies outcomes in patients at standard risk without NPM1 mutations. Journal of Clinical Oncology 36 (14) , pp. 1486-1497. 10.1200/JCO.2017.76.3425

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Abstract

Terms of Use. Journal of Clinical Oncology Log In assignment_turned_inSubmit mail_outlineE-Alerts add_shopping_cartSubscribe OpenAthens/Shibboleth » Advanced Search Newest Articles Issues Special Content Authors Subscribers About ASCO Publications Career Center COVID-19 Journal of Clinical Oncology > List of Issues > Volume 36, Issue 15 > ORIGINAL REPORTS Hematologic Malignancy Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Purchase Rights & Permissions Article has an altmetric score of 27 COMPANION ARTICLES Minimal Residual Disease Testing After Induction Chemotherapy for Acute Myeloid Leukemia: Moving Beyond Prognostication?. April 06, 2018 ARTICLE CITATION DOI: 10.1200/JCO.2017.76.3425 Journal of Clinical Oncology - published online before print March 30, 2018 PMID: 29601212 Measurable Residual Disease at Induction Redefines Partial Response in Acute Myeloid Leukemia and Stratifies Outcomes in Patients at Standard Risk Without NPM1 Mutations Sylvie D. Freeman, Robert K. Hills, Paul Virgo, Naeem Khan, Steve Couzens, Richard Dillon, ... Show More S.D.F. and R.K. H. contributed equally to this work. Abstract Full Text PDF Figures and Tables Supplements Purpose We investigated the effect on outcome of measurable or minimal residual disease (MRD) status after each induction course to evaluate the extent of its predictive value for acute myeloid leukemia (AML) risk groups, including NPM1 wild-type (wt) standard risk, when incorporated with other induction response criteria. Methods As part of the NCRI AML17 trial, 2,450 younger adult patients with AML or high-risk myelodysplastic syndrome had prospective multiparameter flow cytometric MRD (MFC-MRD) assessment. After course 1 (C1), responses were categorized as resistant disease (RD), partial remission (PR), and complete remission (CR) or complete remission with absolute neutrophil count < 1,000/µL or thrombocytopenia < 100,000/μL (CRi) by clinicians, with CR/CRi subdivided by MFC-MRD assay into MRD+ and MRD−. Patients without high-risk factors, including Flt3 internal tandem duplication wt/−NPM1-wt subgroup, received a second daunorubicin/cytosine arabinoside induction; course 2 (C2) was intensified for patients with high-risk factors. Results Survival outcomes from PR and MRD+ responses after C1 were similar, particularly for good- to standard-risk subgroups (5-year overall survival [OS], 27% RD v 46% PR v 51% MRD+ v 70% MRD−; P < .001). Adjusted analyses confirmed significant OS differences between C1 RD versus PR/MRD+ but not PR versus MRD+. CRi after C1 reduced OS in MRD+ (19% CRi v 45% CR; P = .001) patients, with a smaller effect after C2. The prognostic effect of C2 MFC-MRD status (relapse: hazard ratio [HR], 1.88 [95% CI, 1.50 to 2.36], P < .001; survival: HR, 1.77 [95% CI, 1.41 to 2.22], P < .001) remained significant when adjusting for C1 response. MRD positivity appeared less discriminatory in poor-risk patients by stratified analyses. For the NPM1-wt standard-risk subgroup, C2 MRD+ was significantly associated with poorer outcomes (OS, 33% v 63% MRD−, P = .003; relapse incidence, 89% when MRD+ ≥ 0.1%); transplant benefit was more apparent in patients with MRD+ (HR, 0.72; 95% CI, 0.31 to 1.69) than those with MRD− (HR, 1.68 [95% CI, 0.75 to 3.85]; P = .16 for interaction). Conclusion MFC-MRD can improve outcome stratification by extending the definition of partial response after first induction and may help predict NPM1-wt standard-risk patients with poor outcome who benefit from transplant in the first CR.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Centre for Trials Research (CNTRR)
Publisher: American Society of Clinical Oncology
ISSN: 0732-183X
Date of First Compliant Deposit: 25 May 2021
Date of Acceptance: 20 May 2018
Last Modified: 25 May 2021 15:45
URI: http://orca.cardiff.ac.uk/id/eprint/141386

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