{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T16:31:47Z","timestamp":1793118707839,"version":"4.5.0"},"reference-count":24,"publisher":"American Society of Hematology","issue":"21","license":[{"start":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T00:00:00Z","timestamp":1723420800000},"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":[[2024,11,21]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>The European LeukemiaNet (ELN) acute myeloid leukemia (AML) genetic risk classification systems are based on response to intensive chemotherapy; their ability to discriminate outcomes in older patients treated with venetoclax-azacitidine may be suboptimal. This pooled analysis of the phase 3 VIALE-A trial (NCT02993523) and phase 1b study (NCT02203773) examined prognostic stratification according to the 2017 and 2022 ELN risk classifications and derived new molecular signatures differentiating venetoclax-azacitidine\u2013treated patients based on overall survival (OS). Overall, 279 patients treated with venetoclax-azacitidine and 113 patients treated with placebo-azacitidine were analyzed. The ELN 2017 or 2022 prognostic criteria classified most patients as adverse-risk AML (60.2% and 72.8% for venetoclax-azacitidine and 65.5% and 75.2% for placebo-azacitidine, respectively). Although outcomes with venetoclax-azacitidine improved across all ELN risk groups compared with placebo-azacitidine, ELN classification systems poorly discriminated venetoclax-azacitidine outcomes. By applying a bioinformatic algorithm, new molecular signatures were derived differentiating OS outcomes with venetoclax-azacitidine. The mutational status of TP53, FLT3 internal tandem duplication (FLT3-ITD), NRAS, and KRAS categorized patients into higher-, intermediate-, and lower-benefit groups (52%, 25%, and 23% of patients, respectively), each associated with a distinct median OS (26.5 months [95% confidence interval (CI), 20.2-32.7]; 12.1 months [95% CI, 7.3-15.2]; and 5.5 months [95% CI, 2.8-7.6], respectively). ELN prognostic classifiers did not provide clinically meaningful risk stratification of OS outcomes in patients treated with venetoclax-azacitidine. TP53, FLT3-ITD, NRAS, and KRAS mutation status allows the classification of these patients into 3 risk groups with distinct differences in median OS. These trials were registered at www.clinicaltrials.gov as #NCT02993523 and #NCT02203773.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2024024944","type":"journal-article","created":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T16:57:51Z","timestamp":1723481871000},"page":"2211-2222","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":173,"title":["Genetic risk stratification and outcomes among treatment-naive patients with AML treated with venetoclax and azacitidine"],"prefix":"10.1182","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2116-5536","authenticated-orcid":false,"given":"Hartmut","family":"D\u00f6hner","sequence":"first","affiliation":[{"name":"1Department of Internal Medicine III, Ulm University Hospital, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith W.","family":"Pratz","sequence":"additional","affiliation":[{"name":"2Division of Hematology-Oncology, Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA"}],"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":"3Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7514-3298","authenticated-orcid":false,"given":"Andrew H.","family":"Wei","sequence":"additional","affiliation":[{"name":"4Department of Clinical Haematology, Peter MacCallum Cancer Centre, The Royal Melbourne Hospital, Walter and Eliza Hall Institute of Medical Research and The University of Melbourne, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4921-5809","authenticated-orcid":false,"given":"Brian A.","family":"Jonas","sequence":"additional","affiliation":[{"name":"5Division of Malignant Hematology\/Cellular Therapy and Transplantation, Department of Internal Medicine, University of California Davis School of Medicine, Sacramento, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod A.","family":"Pullarkat","sequence":"additional","affiliation":[{"name":"6Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Thirman","sequence":"additional","affiliation":[{"name":"7Department of Medicine, Section of Hematology and Oncology, University of Chicago Medicine, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3332-4525","authenticated-orcid":false,"given":"Christian","family":"R\u00e9cher","sequence":"additional","affiliation":[{"name":"8Service d'H\u00e9matologie, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre C.","family":"Schuh","sequence":"additional","affiliation":[{"name":"9Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil","family":"Babu","sequence":"additional","affiliation":[{"name":"10Division of Clinical Research, Fort Wayne Medical Oncology and Hematology, Fort Wayne, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotong","family":"Li","sequence":"additional","affiliation":[{"name":"11AbbVie Inc, North Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Ku","sequence":"additional","affiliation":[{"name":"12Genentech Inc, South San Francisco, 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