{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T19:08:34Z","timestamp":1793992114378,"version":"4.8.0"},"reference-count":25,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"25","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>As risk stratification for patients with AML treated with lower-intensity venetoclax-based therapy remains suboptimal, we developed and validated a prognostic model integrating clinical, cytogenetic, and molecular features.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We assembled a multinational data set comprising 2,092 adults with newly diagnosed AML treated with hypomethylating agents plus venetoclax (HMA + VEN). One thousand nine hundred eighteen patients with complete data were randomly divided into training (70%) and internal validation (30%) cohorts. Two independent external validation cohorts were assembled (n = 500 and n = 222). Modeling overall survival (OS), Elastic Net regression was applied in 1,000 bootstrap samples from the training cohort to select variables for a Ridge regression, which generated a continuous Prognostic Risk Integration for Survival Modeling (PRISM) score and risk categories based on tertiles (PRISM-3: low, moderate, high). These PRISM indices were then computed for the validation cohorts and compared with the 4-gene classifier (based on mutations in\n                      <jats:italic toggle=\"yes\">FLT3<\/jats:italic>\n                      -ITD,\n                      <jats:italic toggle=\"yes\">N\/KRAS<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      PRISM integrated 17 clinical and genomic variables and demonstrated a linear association with OS. PRISM-3 stratified survival consistently across all cohorts (median OS: 25.1-28.8 months for low risk, 12.5-14.7 months for moderate risk, and 5.8-6.7 months for high risk;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001). Compared with the 4-gene classifier, PRISM-3 reassigned approximately 40% of patients (and &gt;50% of those with favorable risk) and demonstrated significantly better discrimination in validation cohorts (C-index 0.63-0.65\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      0.59-0.61;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>PRISM is a validated prognostic model for patients with AML receiving HMA + VEN that improves survival risk stratification beyond current standard tools and supports individualized, risk-adapted clinical decision making. The model, the PRISM-AML Risk Calculator, is publicly available.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-26-00347","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T19:59:11Z","timestamp":1783022351000},"page":"2422-2434","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":4,"title":["Risk Prognostication After Hypomethylating Agents Combined With Venetoclax in AML: The PRISM Risk Model"],"prefix":"10.1200","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8506-0624","authenticated-orcid":false,"given":"Curtis A.","family":"Lachowiez","sequence":"first","affiliation":[{"name":"Oregon Health and Science University, Portland, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9014-1514","authenticated-orcid":false,"given":"Joshua F.","family":"Zeidner","sequence":"additional","affiliation":[{"name":"University of North Carolina, Lineberger Comprehensive Cancer Center, Chapel Hill, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4971-3576","authenticated-orcid":false,"given":"Jad","family":"Othman","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics, King's College London, London, United Kingdom"},{"name":"University of Sydney, Sydney, NSW, Australia"},{"name":"Haematology Department, Royal North Shore Hospital, St. Leonards, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9425-6936","authenticated-orcid":false,"given":"Andy","family":"Kaempf","sequence":"additional","affiliation":[{"name":"Oregon Health and Science University, Portland, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seongseok","family":"Yun","sequence":"additional","affiliation":[{"name":"Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1682-8657","authenticated-orcid":false,"given":"Ma\u00ebl","family":"Heiblig","sequence":"additional","affiliation":[{"name":"Hematology Department, Lyon-Sud Hospital, Hospices Civils de Lyon, Pierre B\u00e9nite, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5318-9044","authenticated-orcid":false,"given":"Michael","family":"Heuser","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany"},{"name":"Department of Internal Medicine IV, University Hospital Halle (Saale), Martin-Luther-University Halle-Wittenberg, Halle, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabia","family":"Shahswar","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany"},{"name":"Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9243-2662","authenticated-orcid":false,"given":"Rafael","family":"Madero Marroquin","sequence":"additional","affiliation":[{"name":"Section of Hematology-Oncology, Department of Medicine, University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9986-1999","authenticated-orcid":false,"given":"Joseph M.","family":"Cannova","sequence":"additional","affiliation":[{"name":"Section of Hematology-Oncology, Department of Medicine, University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5520-1534","authenticated-orcid":false,"given":"Andrius","family":"\u017du\u010denka","sequence":"additional","affiliation":[{"name":"Hematology and Oncology Department, Faculty of Medicine, and Hematology, Oncology, and Transfusion Medicine Center, National Cancer Center, Vilnius University Hospital Santaros Klinikos, Vilnius University, Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9595-1279","authenticated-orcid":false,"given":"Jennifer","family":"Marvin-Peek","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6831-2567","authenticated-orcid":false,"given":"Jayastu","family":"Senapati","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9156-7912","authenticated-orcid":false,"given":"Yasmin","family":"Abaza","sequence":"additional","affiliation":[{"name":"Leukemia Program, Division of Hematology and Oncology, Robert H. 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