{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T14:05:30Z","timestamp":1774620330313,"version":"3.50.1"},"reference-count":28,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Recently, oral decitabine\/cedazuridine has been approved for the treatment of AML patients who are not eligible for intensive chemotherapy. Although efficacy data on phenotypic features and the prognostic impact of molecular aberrations at diagnosis were reported in the registration study, serial determinations of the mutational landscape during therapy were not reported. In this study, we present data on a subset of five patients in whom molecular markers were monitored during treatment with oral decitabine\/cedazuridine within the registration study. The following observations were made in individual patients. Regarding the changes in the molecular landscape during therapy in four\/five patients, there was no major (&gt;50%) reduction in mutated AML clones. There was only one patient with CRi and more than 50% reduction in the VAF of clones with molecular aberrations, including RAS pathway mutations. We observed a marked drop of blast cells (&gt;50%) in two other patients without changes in the molecular profile. The overall survival was significantly longer in patients with CRi and PR, respectively, as compared to patients with no response. Finally, four\/five (80%) of patients had druggable molecular aberrations at diagnosis, including mutations in IDH2 (2\/5), NPM1 (2\/5), and FLT3 (1\/5). Our results show that in the majority of patients, changes in the genetic profiles are not seen despite decreases in blast cells in some patients. Disease-modifying activity with decreases in mutated clones is rare. Although the exact mechanism behind our findings remains undetermined, they are in line with the proposed effects of HMA on epigenetics in leukemia cells.<\/jats:p>","DOI":"10.3390\/cancers18071093","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T12:45:53Z","timestamp":1774615553000},"page":"1093","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serial Determinations of Molecular Aberrations in Patients with Acute Myeloid Leukemia During Treatment with Oral Decitabine\/Cedazuridine"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1921-7034","authenticated-orcid":false,"given":"Klaus","family":"Geissler","sequence":"first","affiliation":[{"name":"Medical School, Sigmund Freud Private University, Sigmund Freud Platz 3, 1020 Vienna, Austria"},{"name":"Karl Landsteiner Institute for Hematooncological Research, 1020 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriele","family":"Benetka","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pathology and Molecular Pathology, Hospital Horn, 3580 Horn, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maximilian","family":"Prinz-Wohlgenannt","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pathology and Molecular Pathology, Hospital Horn, 3580 Horn, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang R.","family":"Sperr","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hemostaseology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1182\/blood-2016-08-733196","article-title":"Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel","volume":"129","author":"Estey","year":"2017","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1200\/JCO.2009.23.8329","article-title":"Azacitidine Prolongs Overall Survival Compared With Conventional Care Regimens in Elderly Patients with Low Bone Marrow Blast Count Acute Myeloid Leukemia","volume":"28","author":"Fenaux","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S1470-2045(09)70003-8","article-title":"Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: A randomised, open-label, phase III study","volume":"10","author":"Fenaux","year":"2009","journal-title":"Lancet Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1200\/JCO.2002.04.117","article-title":"Randomized Controlled Trial of Azacitidine in Patients with the Myelodysplastic Syndrome: A Study of the Cancer and Leukemia Group B","volume":"20","author":"Silverman","year":"2002","journal-title":"J. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1182\/blood-2015-01-621664","article-title":"International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts","volume":"126","author":"Dombret","year":"2015","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.1002\/cncr.25774","article-title":"Continued azacitidine therapy beyond time of first response improves quality of response in patients with higher-risk myelodysplastic syndromes","volume":"117","author":"Silverman","year":"2011","journal-title":"Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2670","DOI":"10.1200\/JCO.2011.38.9429","article-title":"Multicenter, Randomized, Open-Label, Phase III Trial of Decitabine Versus Patient Choice, with Physician Advice, of Either Supportive Care or Low-Dose Cytarabine for the Treatment of Older Patients with Newly Diagnosed Acute Myeloid Leukemia","volume":"30","author":"Kantarjian","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_8","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."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1182\/blood-2018-08-868752","article-title":"Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia","volume":"133","author":"DiNardo","year":"2019","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1111\/bjh.19741","article-title":"Oral decitabine\/cedazuridine versus intravenous decitabine for acute myeloid leukaemia: A randomised, crossover, registration, pharmacokinetics study","volume":"205","author":"Geissler","year":"2024","journal-title":"Br. J. Haematol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"10767","DOI":"10.1038\/ncomms10767","article-title":"Mutation allele burden remains unchanged in chronic myelomonocytic leukaemia responding to hypomethylating agents","volume":"7","author":"Merlevede","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1053\/j.seminhematol.2019.02.001","article-title":"Can we predict responsiveness to hypomethylating agents in AML?","volume":"56","author":"Stomper","year":"2019","journal-title":"Semin. Hematol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1056\/NEJMoa1408617","article-title":"Age-related clonal hematopoiesis associated with adverse outcomes","volume":"371","author":"Jaiswal","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1056\/NEJMoa1409405","article-title":"Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence","volume":"371","author":"Genovese","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1002\/jha2.527","article-title":"Heterogeneous genetic and non-genetic mechanisms contribute to response and resistance to azacitidine monotherapy","volume":"3","author":"Symeonidou","year":"2022","journal-title":"eJHaem"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1038\/leu.2016.282","article-title":"Dynamic changes in the clonal structure of MDS and AML in response to epigenetic therapy","volume":"31","author":"Uy","year":"2017","journal-title":"Leukemia"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1056\/NEJMoa1605949","article-title":"TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes","volume":"375","author":"Welch","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2408","DOI":"10.1056\/NEJMoa062867","article-title":"Five-Year Follow-up of Patients Receiving Imatinib for Chronic Myeloid Leukemia","volume":"355","author":"Druker","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1186\/s13045-017-0527-7","article-title":"Long-term survival in patients treated with ruxolitinib for myelofibrosis: COMFORT-I and -II pooled analyses","volume":"10","author":"Verstovsek","year":"2017","journal-title":"J. Hematol. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2592","DOI":"10.1038\/s41375-021-01183-8","article-title":"Interferon-alpha for treating polycythemia vera yields improved myelofibrosis-free and overall survival","volume":"35","author":"Krichevsky","year":"2021","journal-title":"Leukemia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1093\/jnci\/93.14.1062","article-title":"Blocking Oncogenic Ras Signaling for Cancer Therapy","volume":"93","author":"Adjei","year":"2001","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2897","DOI":"10.1158\/0008-5472.CAN-14-2860","article-title":"KRAS Genomic Status Predicts the Sensitivity of Ovarian Cancer Cells to Decitabine","volume":"75","author":"Stewart","year":"2015","journal-title":"Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5612","DOI":"10.1158\/0008-5472.CAN-19-0187","article-title":"Predictive Signatures Inform the Effective Repurposing of Decitabine to Treat KRAS\u2013Dependent Pancreatic Ductal Adenocarcinoma","volume":"79","author":"Mottini","year":"2019","journal-title":"Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1111\/bjh.13062","article-title":"Persistence of DNMT 3A mutations at long-term remission in adult patients with AML","volume":"167","author":"Nederby","year":"2014","journal-title":"Br. J. Haematol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1056\/NEJMoa1614359","article-title":"Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation","volume":"377","author":"Stone","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1182\/blood-2017-04-779405","article-title":"Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia","volume":"130","author":"Stein","year":"2017","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1016\/S1470-2045(24)00386-3","article-title":"Ziftomenib in relapsed or refractory acute myeloid leukaemia (KOMET-001): A multicentre, open-label, multi-cohort, phase 1 trial","volume":"25","author":"Wang","year":"2024","journal-title":"Lancet Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1056\/NEJMoa2117344","article-title":"Ivosidenib and Azacitidine in IDH1 -Mutated Acute Myeloid Leukemia","volume":"386","author":"Montesinos","year":"2022","journal-title":"N. Engl. J. Med."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/7\/1093\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T13:00:23Z","timestamp":1774616423000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/7\/1093"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,27]]},"references-count":28,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["cancers18071093"],"URL":"https:\/\/doi.org\/10.3390\/cancers18071093","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,27]]}}}