{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T06:05:51Z","timestamp":1794377151474,"version":"4.9.0"},"reference-count":50,"publisher":"American Society of Hematology","issue":"1","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Acute myeloid leukemia (AML) is a polyclonal malignancy marked by high relapse rates despite initial morphologic remission. Although measurable residual disease (MRD) is an established prognostic tool, increasing evidence supports a role for preemptive, MRD-directed therapy. AML monitoring is hampered by the absence of a universal MRD marker, necessitating a more personalized approach. NPM1 is suited to an MRD-directed strategy because the mutation is AML defining and the monitoring methods are highly sensitive. Critically, rising NPM1mut levels portend clinical relapse with high fidelity, and recent studies demonstrate that venetoclax-based regimens induce rapid and deep MRD responses in a high proportion of patients with NPM1mut MRD relapse. The range of MRD-directed treatment options is expanding and includes FLT3 and menin inhibitors for MRD relapse driven by FLT3-ITD, NPM1mut and KMT2A rearrangements, respectively. To overcome the logistical issue of multiple MRD markers and associated therapies, we have developed a multitarget, multiarm platform trial named INTERCEPT. Novel features include the potential to adaptively expand the range of MRD markers and directed therapies, seamless transition of patients from a local to centralized MRD monitoring framework, a clinical decision rules approach to allocate treatment in a hierarchical and prespecified manner, creation of parallel protocol appendices to enable multiple industry partners to coexist with commercial independence, and development of approaches to minimize the time interval from \u201cMRD relapse to treatment.\u201d The future success of MRD-directed therapy will depend on rapid diagnostic turnaround, coordinated logistics, and innovative clinical trial designs able to keep pace with advances in MRD detection technologies and associated targeted therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025029010","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T20:00:16Z","timestamp":1760731216000},"page":"13-23","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":11,"title":["Measurable residual disease intervention in AML: a new therapeutic horizon"],"prefix":"10.1182","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7514-3298","authenticated-orcid":false,"given":"Andrew H.","family":"Wei","sequence":"first","affiliation":[{"name":"1Department of Haematology, Peter MacCallum Cancer Centre and The Royal Melbourne Hospital, Melbourne, VIC, Australia"},{"name":"2Division of Blood Cells and Blood Cancer, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9787-5908","authenticated-orcid":false,"given":"Harry J.","family":"Iland","sequence":"additional","affiliation":[{"name":"3Institute of Haematology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9003-0390","authenticated-orcid":false,"given":"Courtney D.","family":"DiNardo","sequence":"additional","affiliation":[{"name":"4Department of Leukemia, MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8825-8625","authenticated-orcid":false,"given":"John","family":"Reynolds","sequence":"additional","affiliation":[{"name":"5Department of Clinical Haematology, Australian Centre for Blood Diseases, Monash University and Alfred Hospital, Melbourne, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"7834","key":"2026012115421624300_bib1","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/s41586-020-2864-x","article-title":"Single-cell mutation analysis of clonal evolution in myeloid malignancies","volume":"587","author":"Miles","year":"2020","journal-title":"Nature"},{"issue":"1","key":"2026012115421624300_bib2","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/s41408-024-00996-x","article-title":"How comparable are patient outcomes in the \u201creal-world\u201d with populations studied in pivotal AML trials?","volume":"14","author":"Tiong","year":"2024","journal-title":"Blood Cancer J"},{"issue":"7","key":"2026012115421624300_bib3","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1056\/NEJMoa2012971","article-title":"Azacitidine and venetoclax in previously untreated acute myeloid leukemia","volume":"383","author":"DiNardo","year":"2020","journal-title":"N Engl J Med"},{"issue":"11","key":"2026012115421624300_bib4","first-page":"3543","article-title":"Outcomes and genetic dynamics of acute myeloid leukemia at first relapse","volume":"109","author":"Bataller","year":"2024","journal-title":"Haematologica"},{"issue":"6","key":"2026012115421624300_bib5","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1002\/cyto.b.22144","article-title":"Analytical assay validation for acute myeloid leukemia measurable residual disease assessment by multiparametric flow cytometry","volume":"104","author":"Tettero","year":"2023","journal-title":"Cytometry B Clin Cytom"},{"issue":"1","key":"2026012115421624300_bib6","doi-asserted-by":"crossref","first-page":"e66","DOI":"10.1002\/cpcy.66","article-title":"Immunophenotypic detection of measurable residual (stem cell) disease using LAIP approach in acute myeloid leukemia","volume":"91","author":"Zeijlemaker","year":"2019","journal-title":"Curr Protoc Cytom"},{"issue":"18","key":"2026012115421624300_bib7","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1200\/JCO.23.01599","article-title":"Targeting molecular measurable residual disease and low-blast relapse in AML with venetoclax and low-dose cytarabine: a prospective phase II study (VALDAC)","volume":"42","author":"Tiong","year":"2024","journal-title":"J Clin Oncol"},{"issue":"8","key":"2026012115421624300_bib8","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1038\/s41375-024-02300-z","article-title":"Pre-emptive detection and evolution of relapse in acute myeloid leukemia by flow cytometric measurable residual disease surveillance","volume":"38","author":"McCarthy","year":"2024","journal-title":"Leukemia"},{"issue":"26","key":"2026012115421624300_bib9","doi-asserted-by":"crossref","first-page":"2526","DOI":"10.1056\/NEJMoa2004444","article-title":"Oral azacitidine maintenance therapy for acute myeloid leukemia in first remission","volume":"383","author":"Wei","year":"2020","journal-title":"N Engl J Med"},{"issue":"2","key":"2026012115421624300_bib10","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/s41409-021-01515-3","article-title":"Long-term results and GvHD after prophylactic and preemptive donor lymphocyte infusion after allogeneic stem cell transplantation for acute leukemia","volume":"57","author":"Schmid","year":"2022","journal-title":"Bone Marrow Transpl"},{"issue":"suppl 1","key":"2026012115421624300_bib11","doi-asserted-by":"crossref","first-page":"4335","DOI":"10.1182\/blood-2024-208817","article-title":"Azacytidine and venetoclax as a salvage therapy in measurable residual disease (MRD) relapse post intensive chemotherapy or allogenic stem cell transplantation in acute myeloid leukemia patients: a multicentric study from French Auraml Group [abstract]","volume":"144","author":"Carre","year":"2024","journal-title":"Blood"},{"issue":"12","key":"2026012115421624300_bib12","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1016\/S1470-2045(18)30580-1","article-title":"Measurable residual disease-guided treatment with azacitidine to prevent haematological relapse in patients with myelodysplastic syndrome and acute myeloid leukaemia (RELAZA2): an open-label, multicentre, phase 2 trial","volume":"19","author":"Platzbecker","year":"2018","journal-title":"Lancet Oncol"},{"issue":"suppl 1","key":"2026012115421624300_bib13","doi-asserted-by":"crossref","first-page":"2946","DOI":"10.1182\/blood-2023-184433","article-title":"Recommendations on minimal residual disease monitoring in acute promyelocytic leukemia treated with combination of all-trans retinoic acid and arsenic trioxide [abstract]","volume":"142","author":"Chen","year":"2023","journal-title":"Blood"},{"key":"2026012115421624300_bib14","doi-asserted-by":"crossref","first-page":"614215","DOI":"10.3389\/fonc.2021.614215","article-title":"Role of hematopoietic stem cell transplantation in acute promyelocytic leukemia","volume":"11","author":"Sanz","year":"2021","journal-title":"Front Oncol"},{"issue":"19","key":"2026012115421624300_bib15","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.1182\/blood.2024025154","article-title":"Measurable residual disease and posttransplantation gilteritinib maintenance for patients with FLT3-ITD\u2013mutated AML","volume":"145","author":"Levis","year":"2025","journal-title":"Blood"},{"issue":"suppl 1","key":"2026012115421624300_bib16","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1182\/blood-2024-202895","article-title":"Revumenib as pre-emptive therapy for measurable residual disease in NPM1 mutated or KMT2A-rearranged acute myeloid leukemia: a domain of the multi-arm ALLG AMLM26 intercept platform trial [abstract]","volume":"144","author":"Loo","year":"2024","journal-title":"Blood"},{"issue":"suppl 1","key":"2026012115421624300_bib17","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1182\/blood-2023-178329","article-title":"Clinical characteristics, genetic profile and prognosis of adult acute myeloid leukemia with NUP98 rearrangement [abstract]","volume":"142","author":"Zhu","year":"2023","journal-title":"Blood"},{"issue":"4","key":"2026012115421624300_bib18","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.3324\/haematol.2024.286537","article-title":"Complete remission of NUP98 fusion-positive acute myeloid leukemia with the covalent menin inhibitor BMF-219, icovamenib","volume":"110","author":"Carraway","year":"2025","journal-title":"Haematologica"},{"issue":"26","key":"2026012115421624300_bib19","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1182\/blood.2021013626","article-title":"2021 update on MRD in acute myeloid leukemia: a consensus document from the European LeukemiaNet Working Party","volume":"138","author":"Heuser","year":"2021","journal-title":"Blood"},{"issue":"12","key":"2026012115421624300_bib20","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1182\/blood-2017-09-801498","article-title":"Minimal\/measurable residual disease in AML: a consensus document from the European LeukemiaNet MRD Working Party","volume":"131","author":"Schuurhuis","year":"2018","journal-title":"Blood"},{"issue":"2","key":"2026012115421624300_bib21","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1016\/j.jtct.2023.12.030","article-title":"Optimal prognostic threshold for acute myeloid leukemia (AML) measurable residual disease (MRD) positivity by multiparameter flow cytometry: a report of 2,051 patients from MRC\/NCRI, Gimema, HOVON, and Seattle","volume":"30","author":"Rodr\u00edguez-Arbol\u00ed","year":"2024","journal-title":"Transplant Cell Ther"},{"issue":"5","key":"2026012115421624300_bib22","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1056\/NEJMoa1507471","article-title":"Assessment of minimal residual disease in standard-risk AML","volume":"374","author":"Ivey","year":"2016","journal-title":"N Engl J Med"},{"issue":"9","key":"2026012115421624300_bib23","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1182\/blood.2019002959","article-title":"Molecular MRD status and outcome after transplantation in NPM1-mutated AML","volume":"135","author":"Dillon","year":"2020","journal-title":"Blood"},{"issue":"9","key":"2026012115421624300_bib24","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1038\/s41375-024-02335-2","article-title":"Molecular relapse after first-line intensive therapy in patients with CBF or NPM1-mutated acute myeloid leukemia\u2013a FILO study","volume":"38","author":"Orvain","year":"2024","journal-title":"Leukemia"},{"issue":"24","key":"2026012115421624300_bib25","doi-asserted-by":"crossref","first-page":"2554","DOI":"10.1182\/blood.2024026605","article-title":"Pre-transplant MRD detection of fusion transcripts is strongly prognostic in KMT2A-rearranged acute myeloid leukemia","volume":"144","author":"Loo","year":"2024","journal-title":"Blood"},{"issue":"22","key":"2026012115421624300_bib26","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1182\/blood.2022016567","article-title":"Pretransplant FLT3-ITD MRD assessed by high-sensitivity PCR-NGS determines posttransplant clinical outcome","volume":"140","author":"Loo","year":"2022","journal-title":"Blood"},{"issue":"10","key":"2026012115421624300_bib27","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.1038\/s41375-023-01994-x","article-title":"FLT3 inhibitors as MRD-guided salvage treatment for molecular failure in FLT3 mutated AML","volume":"37","author":"Othman","year":"2023","journal-title":"Leukemia"},{"issue":"12","key":"2026012115421624300_bib28","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1200\/JCO.19.03011","article-title":"Impact of conditioning intensity of allogeneic transplantation for acute myeloid leukemia with genomic evidence of residual disease","volume":"38","author":"Hourigan","year":"2020","journal-title":"J Clin Oncol"},{"issue":"8","key":"2026012115421624300_bib29","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1001\/jamaoncol.2024.0985","article-title":"Measurable residual FLT3 internal tandem duplication before allogeneic transplant for acute myeloid leukemia","volume":"10","author":"Dillon","year":"2024","journal-title":"JAMA Oncol"},{"issue":"3","key":"2026012115421624300_bib30","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1182\/blood.2023022697","article-title":"Clonal relapse dynamics in acute myeloid leukemia following allogeneic hematopoietic cell transplantation","volume":"144","author":"Wienecke","year":"2024","journal-title":"Blood"},{"issue":"10","key":"2026012115421624300_bib31","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.3324\/haematol.2011.044388","article-title":"Minimal residual disease-directed preemptive treatment with azacitidine in patients with NPM1-mutant acute myeloid leukemia and molecular relapse","volume":"96","author":"Sockel","year":"2011","journal-title":"Haematologica"},{"issue":"4","key":"2026012115421624300_bib32","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1111\/ijlh.13608","article-title":"Comparison of RNA-and DNA-based methods for measurable residual disease analysis in NPM1-mutated acute myeloid leukemia","volume":"43","author":"Pettersson","year":"2021","journal-title":"Int J Lab Hematol"},{"issue":"5","key":"2026012115421624300_bib33","doi-asserted-by":"crossref","first-page":"e346","DOI":"10.1016\/S2352-3026(25)00037-7","article-title":"Molecular monitoring versus standard clinical care in younger adults with acute myeloid leukaemia: results from the UK NCRI AML17 and AML19 randomised, controlled, phase 3 trials","volume":"12","author":"Potter","year":"2025","journal-title":"Lancet Haematol"},{"issue":"11","key":"2026012115421624300_bib34","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1182\/blood.2019003988","article-title":"Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML","volume":"135","author":"DiNardo","year":"2020","journal-title":"Blood"},{"issue":"7","key":"2026012115421624300_bib35","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1182\/bloodadvances.2019001267","article-title":"Outcomes of older patients with NPM1-mutated AML: current treatments and the promise of venetoclax-based regimens","volume":"4","author":"Lachowiez","year":"2020","journal-title":"Blood Adv"},{"issue":"24","key":"2026012115421624300_bib36","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1182\/blood.2020004856","article-title":"Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial","volume":"135","author":"Wei","year":"2020","journal-title":"Blood"},{"issue":"30","key":"2026012115421624300_bib37","doi-asserted-by":"crossref","first-page":"3506","DOI":"10.1200\/JCO.20.00572","article-title":"Chemotherapy and venetoclax in elderly acute myeloid leukemia trial (CAVEAT): a phase Ib dose-escalation study of venetoclax combined with modified intensive chemotherapy","volume":"38","author":"Chua","year":"2020","journal-title":"J Clin Oncol"},{"issue":"4","key":"2026012115421624300_bib38","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1182\/blood.2023021579","article-title":"Molecular MRD is strongly prognostic in patients with NPM1-mutated AML receiving venetoclax-based nonintensive therapy","volume":"143","author":"Othman","year":"2024","journal-title":"Blood"},{"issue":"6","key":"2026012115421624300_bib39","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1111\/bjh.16722","article-title":"Venetoclax induces rapid elimination of NPM1 mutant measurable residual disease in combination with low-intensity chemotherapy in acute myeloid leukaemia","volume":"192","author":"Tiong","year":"2021","journal-title":"Br J Haematol"},{"issue":"2","key":"2026012115421624300_bib40","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1182\/bloodadvances.2023011106","article-title":"Venetoclax\u2013based low intensity therapy in molecular failure of NPM1-mutated AML","volume":"8","author":"Jimenez-Chillon","year":"2024","journal-title":"Blood Adv"},{"issue":"3","key":"2026012115421624300_bib41","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1111\/bjh.18887","article-title":"A venetoclax and azacitidine bridge-to-transplant strategy for NPM1-mutated acute myeloid leukaemia in molecular failure","volume":"202","author":"Sartor","year":"2023","journal-title":"Br J Haematol"},{"issue":"suppl 1","key":"2026012115421624300_bib42","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1182\/blood-2024-205592","article-title":"Real-world multicenter evaluation of venetoclax and azacitidine for molecular relapse after first line intensive chemotherapy in patients with NPM1 mutated or core binding factor (CBF) AML. a Filo study [abstract]","volume":"144","author":"Higu\u00e9","year":"2024","journal-title":"Blood"},{"issue":"6","key":"2026012115421624300_bib43","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1182\/bloodadvances.2022008316","article-title":"Clinical outcomes associated with NPM1 mutations in patients with relapsed or refractory AML","volume":"7","author":"Issa","year":"2023","journal-title":"Blood Adv"},{"issue":"14","key":"2026012115421624300_bib44","doi-asserted-by":"crossref","first-page":"7912","DOI":"10.3390\/ijms25147912","article-title":"Evaluation of a new closed-system automated RT-qPCR assay for the rapid detection and monitoring of common nucleophosmin mutations in patients with acute myeloid leukemia","volume":"25","author":"Press","year":"2024","journal-title":"Int J Mol Sci"},{"issue":"3","key":"2026012115421624300_bib45","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1038\/s41375-018-0363-y","article-title":"New study-designs to address the clinical complexity of acute myeloid leukemia","volume":"33","author":"Estey","year":"2019","journal-title":"Leukemia"},{"issue":"3","key":"2026012115421624300_bib46","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1111\/rssc.12089","article-title":"Bayesian optimal interval designs for phase I clinical trials","volume":"64","author":"Liu","year":"2015","journal-title":"J R Stat Soc C"},{"issue":"17","key":"2026012115421624300_bib47","doi-asserted-by":"crossref","first-page":"4291","DOI":"10.1158\/1078-0432.CCR-16-0592","article-title":"Bayesian optimal interval design: a simple and well-performing design for phase I oncology trials","volume":"22","author":"Yuan","year":"2016","journal-title":"Clin Cancer Res"},{"issue":"13","key":"2026012115421624300_bib48","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1002\/sim.3997","article-title":"A proof of concept phase II non-inferiority criterion","volume":"30","author":"Neuenschwander","year":"2011","journal-title":"Stat Med"},{"issue":"5","key":"2026012115421624300_bib49","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1177\/1740774518770661","article-title":"Beyond p-values: a phase II dual-criterion design with statistical significance and clinical relevance","volume":"15","author":"Roychoudhury","year":"2018","journal-title":"Clin Trials"},{"issue":"2","key":"2026012115421624300_bib50","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1080\/00031305.2016.1154108","article-title":"The ASA statement on p-values: context, process, and purpose","volume":"70","author":"Wasserstein","year":"2016","journal-title":"Am Statistician"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/147\/1\/13\/2478426\/blood_bld-2025-029010-c-main.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/147\/1\/13\/2478426\/blood_bld-2025-029010-c-main.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T20:42:27Z","timestamp":1769028147000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/147\/1\/13\/547836\/Measurable-residual-disease-intervention-in-AML-a"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,1]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1,1]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2025029010","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,1,1]]},"published":{"date-parts":[[2026,1,1]]}}}