{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T04:38:54Z","timestamp":1793335134262,"version":"4.5.0"},"reference-count":17,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"23","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2025,8,10]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>\n                      Azacitidine and venetoclax is a standard frontline treatment regimen for newly diagnosed older adults with AML; however, long-term outcomes remain poor. Revumenib is an oral menin inhibitor with clinical activity in AML patients with nucleophosmin-1 mutation (\n                      <jats:italic toggle=\"yes\">NPM1m<\/jats:italic>\n                      ) or lysine methyltransferase 2A rearrangements (\n                      <jats:italic toggle=\"yes\">KMT2Ar<\/jats:italic>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We conducted a phase I dose-escalation and expansion study of azacitidine, venetoclax, and revumenib at two dose levels (113 mg or 163 mg orally every 12 hours in combination with strong cytochrome P450 inhibitor azoles) in patients aged 60 years and older newly diagnosed with AML with\n                      <jats:italic toggle=\"yes\">NPM1m<\/jats:italic>\n                      or\n                      <jats:italic toggle=\"yes\">KMT2Ar<\/jats:italic>\n                      (ClinicalTrials.gov identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT03013998\">NCT03013998<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Overall, 43 patients were enrolled and treated. There was no maximal tolerated dose identified. Differentiation syndrome was present in eight (19%) patients and QTc Fridericia prolongation was present in 19 (44%) patients, and neither required permanent discontinuation of revumenib. The overall response rate with an intention-to-treat population was 88.4% (95% CI, 74.9 to 96.1;\n                      <jats:italic toggle=\"yes\">NPM1m<\/jats:italic>\n                      : 85.3%;\n                      <jats:italic toggle=\"yes\">KMT2Ar<\/jats:italic>\n                      : 100%), the rate of composite complete remission (complete remission [CR] + CR with partial or incomplete hematologic recovery) was 81.4% (95% CI, 66.6 to 91.6; NPM1m: 79.4%; KMT2Ar: 88.9%), and the rate of CR was 67.4% (95% CI, 51.5 to 80.9;\n                      <jats:italic toggle=\"yes\">NPM1m<\/jats:italic>\n                      : 65%;\n                      <jats:italic toggle=\"yes\">KMT2Ar<\/jats:italic>\n                      : 78%). No patient had refractory disease after 1-2 cycles of treatment. The median time to first response was 28 days, and 84% of responders achieved remission within the first cycle. All 37 patients evaluated had no evidence of measurable residual disease by a centralized flow cytometry assay.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      In older adults newly diagnosed with\n                      <jats:italic toggle=\"yes\">NPM1m<\/jats:italic>\n                      or\n                      <jats:italic toggle=\"yes\">KMT2Ar<\/jats:italic>\n                      AML, the combination of azacitidine, venetoclax, and revumenib was able to be safely administered with high rates of CR and clinical activity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-00914","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T11:55:18Z","timestamp":1749729318000},"page":"2606-2615","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":62,"title":["Azacitidine, Venetoclax, and Revumenib for Newly Diagnosed\n                    <i>NPM1<\/i>\n                    -Mutated or\n                    <i>KMT2A<\/i>\n                    -Rearranged AML"],"prefix":"10.1200","volume":"43","clinical-trial-number":[{"clinical-trial-number":"nct03013998","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9014-1514","authenticated-orcid":true,"given":"Joshua F.","family":"Zeidner","sequence":"first","affiliation":[{"name":"Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara L.","family":"Lin","sequence":"additional","affiliation":[{"name":"University of Kansas Medical Center, Kansas City, KS"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9477-4581","authenticated-orcid":true,"given":"Rina Li","family":"Welkie","sequence":"additional","affiliation":[{"name":"The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Curran","sequence":"additional","affiliation":[{"name":"University of Cincinnati, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Koenig","sequence":"additional","affiliation":[{"name":"The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8349-9200","authenticated-orcid":true,"given":"Wendy","family":"Stock","sequence":"additional","affiliation":[{"name":"University of Chicago Comprehensive Cancer Center, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazan F.","family":"Madanat","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center, Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronan","family":"Swords","sequence":"additional","affiliation":[{"name":"Knight Cancer Institute, Oregon Health &amp; Science University, Portland, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria R.","family":"Baer","sequence":"additional","affiliation":[{"name":"University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0111-7465","authenticated-orcid":true,"given":"William","family":"Blum","sequence":"additional","affiliation":[{"name":"Winship Cancer Institute of Emory University, Atlanta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8992-9390","authenticated-orcid":true,"given":"Eytan M.","family":"Stein","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5060-0384","authenticated-orcid":true,"given":"Rebecca L.","family":"Olin","sequence":"additional","affiliation":[{"name":"University of California San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Schiller","sequence":"additional","affiliation":[{"name":"David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Nichols","sequence":"additional","affiliation":[{"name":"Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olatoyosi","family":"Odenike","sequence":"additional","affiliation":[{"name":"University of Chicago Comprehensive Cancer Center, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8844-2345","authenticated-orcid":true,"given":"Elie","family":"Traer","sequence":"additional","affiliation":[{"name":"Knight Cancer Institute, Oregon Health &amp; 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