{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T05:24:21Z","timestamp":1794029061166,"version":"4.8.0"},"reference-count":35,"publisher":"American Society of Hematology","issue":"17","license":[{"start":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T00:00:00Z","timestamp":1659398400000},"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":[[2022,10,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Treatment results for patients with newly diagnosed FMS-like tyrosine kinase 3 (FLT3)-mutated (FLT3mut+) acute myeloid leukemia (AML) ineligible for intensive chemotherapy are disappointing. This multicenter, open-label, phase 3 trial randomized (2:1) untreated adults with FLT3mut+ AML ineligible for intensive induction chemotherapy to receive gilteritinib (120 mg\/d orally) and azacitidine (GIL\u00a0+ AZA) or azacitidine (AZA) alone. The primary end point was overall survival (OS). At the interim analysis (August 26, 2020), a total of 123 patients were randomized to treatment (GIL\u00a0+ AZA, n\u00a0= 74; AZA, n\u00a0=\u00a049). Subsequent AML therapy, including FLT3 inhibitors, was received by 20.3% (GIL\u00a0+ AZA) and 44.9% (AZA) of patients. Median OS was 9.82 (GIL\u00a0+ AZA) and 8.87 (AZA) months (hazard ratio, 0.916; 95% CI, 0.529-1.585; P\u00a0= .753). The study was closed based on the protocol-specified boundary for futility. Median event-free survival was 0.03 month in both arms. Event-free survival defined by using composite complete remission (CRc) was 4.53 months for GIL\u00a0+ AZA and 0.03 month for AZA (hazard ratio, 0.686; 95% CI, 0.433-1.087; P\u00a0= .156). CRc rates were 58.1% (GIL\u00a0+ AZA) and 26.5% (AZA) (difference, 31.4%; 95% CI, 13.1-49.7; P\u00a0&amp;lt; .001). Adverse event (AE) rates were similar for GIL\u00a0+ AZA (100%) and AZA (95.7%); grade \u22653 AEs were 95.9% and 89.4%, respectively. Common AEs with GIL\u00a0+ AZA included pyrexia (47.9%) and diarrhea (38.4%). Gilteritinib steady-state trough concentrations did not differ between GIL\u00a0+ AZA and gilteritinib. GIL\u00a0+ AZA resulted in significantly higher CRc rates, although similar OS compared with AZA. Results support the safety\/tolerability and clinical activity of upfront therapy with GIL\u00a0+ AZA in older\/unfit patients with FLT3mut+ AML. This trial was registered at www.clinicaltrials.gov as #NCT02752035.<\/jats:p>","DOI":"10.1182\/blood.2021014586","type":"journal-article","created":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T15:10:03Z","timestamp":1659453003000},"page":"1845-1857","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":144,"title":["Phase 3 trial of gilteritinib plus azacitidine vs azacitidine for newly diagnosed\n                    <i>FLT3<\/i>\n                    mut+ AML ineligible for intensive chemotherapy"],"prefix":"10.1182","volume":"140","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8644-0968","authenticated-orcid":false,"given":"Eunice S.","family":"Wang","sequence":"first","affiliation":[{"name":"1RoswellPark Comprehensive Cancer Center, Buffalo, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3275-5593","authenticated-orcid":false,"given":"Pau","family":"Montesinos","sequence":"additional","affiliation":[{"name":"2Hospital Universitari i Polit\u00e8cnic La Fe, Valencia & CIBERONC, Instituto Carlos III, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9089-8816","authenticated-orcid":false,"given":"Mark D.","family":"Minden","sequence":"additional","affiliation":[{"name":"3Princess Margaret Hospital, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7060-1675","authenticated-orcid":false,"given":"Je-Hwan","family":"Lee","sequence":"additional","affiliation":[{"name":"4Asan Medical Center, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Heuser","sequence":"additional","affiliation":[{"name":"5Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoki","family":"Naoe","sequence":"additional","affiliation":[{"name":"6National Hospital Organization Nagoya Medical Center, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Chien","family":"Chou","sequence":"additional","affiliation":[{"name":"7National Taiwan University Hospital, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamel","family":"Laribi","sequence":"additional","affiliation":[{"name":"8Hematology Department, Centre Hospitalier Du Mans, Le Mans, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Esteve","sequence":"additional","affiliation":[{"name":"9Hospital Clinic de Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica K.","family":"Altman","sequence":"additional","affiliation":[{"name":"10Robert H. Lurie Comprehensive Cancer Center, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violaine","family":"Havelange","sequence":"additional","affiliation":[{"name":"11Cliniques Universitaires St. Luc, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Marie","family":"Watson","sequence":"additional","affiliation":[{"name":"12Liverpool Hospital, Liverpool, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6058-515X","authenticated-orcid":false,"given":"Carlo","family":"Gambacorti-Passerini","sequence":"additional","affiliation":[{"name":"13University of Milano-Bicocca, Monza, Italy"},{"name":"14Hematology Division, ASST Monza, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8691-4310","authenticated-orcid":false,"given":"Elzbieta","family":"Patkowska","sequence":"additional","affiliation":[{"name":"15Hematology Department, Institute of Hematology and Transfusion Medicine, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shufang","family":"Liu","sequence":"additional","affiliation":[{"name":"16Astellas Pharma US, Northbrook, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruishan","family":"Wu","sequence":"additional","affiliation":[{"name":"16Astellas Pharma US, Northbrook, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisha","family":"Philipose","sequence":"additional","affiliation":[{"name":"16Astellas Pharma US, Northbrook, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2512-1661","authenticated-orcid":false,"given":"Jason 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