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In this phase I study, previously untreated Japanese patients with acute myeloid leukemia (AML) or high\u2010risk myelodysplastic syndromes were treated with glasdegib (100\u2009mg once daily) combinations: low\u2010dose cytarabine (20\u2009mg twice daily; cohort 1, <jats:italic>n\u2009=<\/jats:italic>\u20096; expansion cohort, <jats:italic>n\u2009=<\/jats:italic>\u200915); daunorubicin and cytarabine (60\u2009mg\/m<jats:sup>2<\/jats:sup> i.v.; cohort 2, <jats:italic>n\u2009=<\/jats:italic>\u20096); or azacitidine (100\u2009mg\/m<jats:sup>2<\/jats:sup> i.v.; cohort 3, <jats:italic>n\u2009=<\/jats:italic>\u20096). Patients, except cohort 2, were ineligible for intensive chemotherapy. The primary end\u2010point was dose\u2010limiting toxicity in cohorts 1\u20133 and disease\u2010modifying response in the expansion cohort. Disease\u2010modifying response rate was tested with the null hypothesis of 6.8%, which was set based on the results from the phase II BRIGHT AML 1003 study (NCT01546038). No dose\u2010limiting toxicities were observed in cohorts 1 or 3; one patient in cohort 2 experienced a dose\u2010limiting toxicity of grade 3 erythroderma. The most common grade \u22653 treatment\u2010related adverse events were neutropenia and thrombocytopenia (66.7% each) in cohort 1 and thrombocytopenia (60.0%) in the expansion cohort. In the expansion cohort, the disease\u2010modifying response rate was 46.7% (90% confidence interval, 24.4\u201370.0; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), with all patients achieving either a complete response or complete response with incomplete blood count recovery. Median overall survival was 13.9\u2009months. In this study, the primary disease\u2010modifying response end\u2010point with glasdegib plus low\u2010dose cytarabine was met. The study confirms the safety and efficacy of glasdegib plus low\u2010dose cytarabine in Japanese patients with AML ineligible for intensive chemotherapy.<\/jats:p>","DOI":"10.1111\/cas.16054","type":"journal-article","created":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T07:03:45Z","timestamp":1707375825000},"page":"1250-1260","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Glasdegib with intensive\/nonintensive chemotherapy in Japanese patients with untreated acute myeloid leukemia or high\u2010risk myelodysplastic syndromes"],"prefix":"10.1111","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9129-8057","authenticated-orcid":false,"given":"Koji","family":"Izutsu","sequence":"first","affiliation":[{"name":"Department of Hematology National Cancer Center Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kumi","family":"Ubukawa","sequence":"additional","affiliation":[{"name":"Department of Hematology, Nephrology and Rheumatology Akita University Hospital  Akita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takanobu","family":"Morishita","sequence":"additional","affiliation":[{"name":"Department of Hematology Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital  Nagoya Aichi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasushi","family":"Onishi","sequence":"additional","affiliation":[{"name":"Department of Hematology Tohoku University Hospital  Sendai Miyagi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenichi","family":"Ishizawa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III Yamagata University Hospital  Yamagata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosuke","family":"Fujii","sequence":"additional","affiliation":[{"name":"Pfizer R&amp;D Japan  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuyuki","family":"Kimura","sequence":"additional","affiliation":[{"name":"Pfizer R&amp;D Japan  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miyuu","family":"Yokochi","sequence":"additional","affiliation":[{"name":"Pfizer R&amp;D Japan  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoki","family":"Naoe","sequence":"additional","affiliation":[{"name":"National Hospital Organization Nagoya Medical Center  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,2,7]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.55.1564"},{"issue":"16","key":"e_1_2_12_3_1","first-page":"S347","article-title":"Unmet clinical needs and economic burden of disease in the treatment landscape of acute myeloid leukemia","volume":"24","author":"Wiese M","year":"2018","journal-title":"Am J Manag Care"},{"key":"e_1_2_12_4_1","unstructured":"Daurismo.Prescribing information. 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