{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:12:00Z","timestamp":1792012320328,"version":"4.4.0"},"reference-count":30,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"13","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2024,5,1]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Azacitidine plus venetoclax is a standard of care for patients with newly diagnosed AML who are unfit for intensive chemotherapy. However, FLT3 mutations are a common mechanism of resistance to this regimen. The addition of gilteritinib, an oral FLT3 inhibitor, to azacitidine and venetoclax may improve outcomes in patients with FLT3-mutated AML.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>This phase I\/II study evaluated azacitidine, venetoclax, and gilteritinib in two cohorts: patients with (1) newly diagnosed FLT3-mutated AML who were unfit for intensive chemotherapy or (2) relapsed\/refractory FLT3-mutated AML (ClinicalTrials.gov identifier: NCT04140487 ). The primary end points were the maximum tolerated dose of gilteritinib (phase I) and the combined complete remission (CR)\/CR with incomplete hematologic recovery (CRi) rate (phase II).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Fifty-two patients were enrolled (frontline [n = 30]; relapsed\/refractory [n = 22]). The recommended phase II dose was gilteritinib 80 mg once daily in combination with azacitidine and venetoclax. In the frontline cohort, the median age was 71 years and 73% of patients had an FLT3-internal tandem duplication (ITD) mutation. The CR\/CRi rate was 96% (CR, 90%; CRi, 6%). Sixty-five percent of evaluable patients achieved FLT3-ITD measurable residual disease &lt;5 \u00d7 10\n                      <jats:sup>\u20135<\/jats:sup>\n                      within four cycles. With a median follow-up of 19.3 months, the median relapse-free survival (RFS) and overall survival (OS) have not been reached and the 18-month RFS and OS rates are 71% and 72%, respectively. In the relapsed\/refractory cohort, the CR\/CRi rate was 27%; nine additional patients (41%) achieved a morphologic leukemia\u2013free state. The most common grade 3 or higher nonhematologic adverse events were infection (62%) and febrile neutropenia (38%), which were more frequent in the relapsed\/refractory cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>The combination of azacitidine, venetoclax, and gilteritinib resulted in high rates of CR\/CRi, deep FLT3 molecular responses, and encouraging survival in newly diagnosed FLT3-mutated AML. Myelosuppression was manageable with mitigative dosing strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.23.01911","type":"journal-article","created":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T15:59:16Z","timestamp":1706284756000},"page":"1499-1508","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":197,"title":["Azacitidine, Venetoclax, and Gilteritinib in Newly Diagnosed and Relapsed or Refractory\n                    <i>FLT3<\/i>\n                    -Mutated AML"],"prefix":"10.1200","volume":"42","clinical-trial-number":[{"clinical-trial-number":"nct04140487","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2983-2738","authenticated-orcid":false,"given":"Nicholas J.","family":"Short","sequence":"first","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, 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