{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T15:44:39Z","timestamp":1786549479541,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Quizartinib is a FMS\u2010like tyrosine kinase 3 (FLT3) inhibitor indicated for\n                    <jats:italic>FLT3<\/jats:italic>\n                    internal tandem duplication (\n                    <jats:italic>FLT3<\/jats:italic>\n                    \u2010ITD)\u2013positive acute myeloid leukemia (AML). We aimed to evaluate quizartinib resistance mechanisms, in addition to efficacy and safety outcomes, in patients with relapsed or refractory\n                    <jats:italic>FLT3<\/jats:italic>\n                    \u2010ITD\u2013positive AML. This multicenter, single\u2010arm study in Japan (jRCTs071200015) enrolled 18 patients between May 2020 and December 2022. Of these, 15 patients received oral quizartinib (up to 53\u2009mg once daily) for up to 12\u2009cycles of 28\u2009days each, then were followed for 12\u2009months. The primary endpoint was to evaluate the type and rate of quizartinib resistance mutations; secondary endpoints included composite complete remission (CRc) rate, overall response rate (ORR), hematopoietic stem cell transplantation (HSCT) rate, relapse\u2010free survival (RFS), overall survival (OS), and adverse events (AEs). Among seven evaluable patients, acquired mutations were detected in four patients (\n                    <jats:italic>NF1<\/jats:italic>\n                    [R2616X],\n                    <jats:italic>CSF3R<\/jats:italic>\n                    [Q754X],\n                    <jats:italic>NRAS<\/jats:italic>\n                    [G13R], and\n                    <jats:italic>FLT3<\/jats:italic>\n                    [D835Y] in one patient each), while loss of\n                    <jats:italic>FLT3<\/jats:italic>\n                    \u2010ITD was observed in two patients. In efficacy analyses (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200915), CRc rate was 66.7% (95% confidence interval [CI], 38.4\u201388.2), ORR was 73.3% (44.9\u201392.2), and median OS was 13.6\u2009months (5.4\u2013not evaluable). Three patients (20.0%) received HSCT directly after quizartinib; in these patients, median RFS was 8.5\u2009months (95% CI, 6.2\u2013not evaluable). Grade \u2265\u20093 non\u2010hematologic AEs and grade 1 QT prolongation were each reported in three patients (20.0%). These data offer additional information on potential resistance mechanisms in patients with relapsed or refractory\n                    <jats:italic>FLT3<\/jats:italic>\n                    \u2010ITD\u2013positive AML.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    Japan Registry of Clinical Trials (jRCTs071200015).\n                  <\/jats:p>","DOI":"10.1111\/cas.70485","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T14:45:40Z","timestamp":1786545940000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Quizartinib Resistance Mutations and Treatment Outcomes in Relapsed or Refractory\n                    <scp>FLT3<\/scp>\n                    \u2010\n                    <scp>ITD<\/scp>\n                    \u2013Positive\n                    <scp>AML<\/scp>"],"prefix":"10.1111","author":[{"given":"Yuichiro","family":"Semba","sequence":"first","affiliation":[{"name":"Department of Medicine and Biosystemic Science Kyushu University Graduate School of Medicine  Fukuoka Japan"},{"name":"Division of Precision Medicine Kyushu University Graduate School of Medical Science  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6533-1594","authenticated-orcid":false,"given":"Toshihiro","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Department of Hematology, Faculty of Medicine Institute of Medical Pharmaceutical and Health Sciences, Kanazawa University  Kanazawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senji","family":"Kasahara","sequence":"additional","affiliation":[{"name":"Department of Hematology Gifu Municipal Hospital  Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshikane","family":"Kikushige","sequence":"additional","affiliation":[{"name":"Division of Precision Medicine Kyushu University Graduate School of Medical Science  Fukuoka Japan"},{"name":"Center for Cellular and Molecular Medicine Kyushu University Hospital  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Hematology Gifu Municipal Hospital  Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goichi","family":"Yoshimoto","sequence":"additional","affiliation":[{"name":"Department of Hematology Saga Prefecture Medical Center Koseikan  Saga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichi","family":"Ota","sequence":"additional","affiliation":[{"name":"Department of Hematology Sapporo Hokuyu Hospital  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Hematology NHO Shibukawa Medical Center  Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8910-0021","authenticated-orcid":false,"given":"Yuho","family":"Najima","sequence":"additional","affiliation":[{"name":"Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Hosoi","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology Wakayama Medical University  Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daigo","family":"Niiya","sequence":"additional","affiliation":[{"name":"Department of Hematology Japanese Red Cross Okayama Hospital  Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5815-4585","authenticated-orcid":false,"given":"Koji","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science Kyushu University Graduate School of Medicine  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4795-121X","authenticated-orcid":false,"given":"Koji","family":"Nagafuji","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine Kurume University Hospital  Kurume Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Akasaka","sequence":"additional","affiliation":[{"name":"Department of Hematology Tenri Hospital  Tenri Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiko","family":"Kamimura","sequence":"additional","affiliation":[{"name":"Department of Hematology Harasanshin Hospital  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Takita","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Co., Ltd.  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