{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T03:50:24Z","timestamp":1789444224348,"version":"build-2803163510"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,12,10]],"date-time":"2023-12-10T00:00:00Z","timestamp":1702166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Venetoclax + hypomethylating agent (Ven\u2010HMA) is currently the standard frontline therapy for older\/unfit patients with newly diagnosed acute myeloid leukemia (ND\u2010AML). Our objective in the current retrospective study of 301 adult patients (median age 73\u2009years; 62% de novo) with ND\u2010AML was to identify molecular predictors of treatment response to Ven\u2010HMA and survival; European LeukemiaNet (ELN) genetic risk assignment was favorable 15%, intermediate 16%, and adverse 69%. Complete remission, with (CR) or without (CRi), count recovery, was documented in 182 (60%) patients. In multivariable analysis, inclusive of mutations only, \u201cfavorable\u201d predictors of CR\/CRi were\n                    <jats:italic>NPM1<\/jats:italic>\n                    (86% vs. 56%),\n                    <jats:italic>IDH2<\/jats:italic>\n                    (80% vs. 58%), and\n                    <jats:italic>DDX41<\/jats:italic>\n                    (100% vs. 58%) and \u201cunfavorable\u201d\n                    <jats:italic>TP53<\/jats:italic>\n                    (40% vs. 67%),\n                    <jats:italic>FLT3\u2010<\/jats:italic>\n                    ITD (36% vs. 63%), and\n                    <jats:italic>RUNX1<\/jats:italic>\n                    (44% vs. 64%) mutations; significance was sustained for each mutation after adjustment for age, karyotype, and therapy\u2010related qualification. CR\/CRi rates ranged from 36%, in the presence of unfavorable and absence of favorable mutation, to 91%, in the presence of favorable and absence of unfavorable mutation. At median follow\u2010up of 8.5\u2009months, 174 deaths and 41 allogeneic stem cell transplants (ASCT) were recorded. In multivariable analysis, risk factors for inferior survival included failure to achieve CR\/CRi (HR 3.4, 95% CI 2.5\u20134.8), adverse karyotype (1.6, 1.1\u20132.6),\n                    <jats:italic>TP53<\/jats:italic>\n                    mutation (1.6, 1.0\u20132.4), and absence of\n                    <jats:italic>IDH2<\/jats:italic>\n                    mutation (2.2, 1.0\u20134.7); these risk factors were subsequently applied to construct an HR\u2010weighted risk model that performed better than the ELN genetic risk model (AIC 1661 vs. 1750): low (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009130; median survival 28.9\u2009months), intermediate (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009105; median 9.6\u2009months), and high (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200966; median 3.1\u2009months;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u2009.001); survival in each risk category was significantly upgraded by ASCT. The current study identifies genotype signatures for predicting response and proposes a 3\u2010tiered, CR\/CRi\u2010based, and genetics\u2010enhanced survival model for AML patients receiving upfront therapy with Ven\u2010HMA.\n                  <\/jats:p>","DOI":"10.1002\/ajh.27138","type":"journal-article","created":{"date-parts":[[2023,12,10]],"date-time":"2023-12-10T09:00:26Z","timestamp":1702198826000},"page":"193-202","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["Venetoclax and hypomethylating agent combination therapy in newly diagnosed acute myeloid leukemia: Genotype signatures for response and survival among 301 consecutive patients"],"prefix":"10.1002","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9104-6172","authenticated-orcid":false,"given":"Naseema","family":"Gangat","sequence":"first","affiliation":[{"name":"Division of Hematology Mayo Clinic  Rochester Minnesota 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