FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) mutations in patients with acute myeloid leukemia (AML) are associated with early relapse and poor survival. This multicenter, single-arm, two-stage phase 2 study (NCT02984995) was conducted to evaluate the efficacy and safety of quizartinib hydrochloride (initial dose 20/30 mg/day), an oral, highly potent, selective FLT3 inhibitor in Japanese patients (median age 65 years) with FLT3-ITD positive relapsed/refractory (R/R) AML. The composite complete remission (CRc) rate (primary endpoint) was 53.8% (90% confidence interval 36.2–70.8%) for evaluable patients in the efficacy analysis set. The median duration of CRc and overall survival was 16.1 weeks and 34.1 weeks, respectively. The most frequent treatment-emergent adverse events (TEAEs) were febrile neutropenia (43.2%), platelet count decreased (37.8%), and QT prolonged (35.1%). Two (5.4%) patients experienced TEAEs associated with treatment discontinuation. All serious TEAEs (45.9%), except febrile neutropenia (16.2%), were reported in ≤ 2 patients. The incidence of QTcF 451–480 ms and 481–500 ms was 37.8% and 2.7%, respectively. No QTcF > 500 ms, events of torsade de pointes or arrhythmia with clinical symptoms were reported. Quizartinib monotherapy was well tolerated and resulted in clinically meaningful reductions in blast count in Japanese patients with FLT3-ITD R/R AML.
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The main data of this manuscript were previously presented at the 80th Annual Meeting of the Japanese Society of Hematology (October 12–14, 2018, Osaka, Japan). This study was sponsored by Daiichi Sankyo Co., Ltd. Medical writing and editorial assistance was provided by Dr. Deepali Garg, MBBS, PGDHA, of Cactus Communications and was funded by Daiichi Sankyo Co., Ltd.
Conflict of interest
KU has received honoraria and lecture fees from Novartis and research funding from Fujimoto, Astellas, Otsuka, Sumitomo Dainippon, Kyowa Hakko Kirin, GlaxoSmithKline, Sanofi, Shire, SymBio, Celgene, Daiichi Sankyo, Boehringer Ingelheim, Pfizer, and Janssen, and speakers bureau from Novartis, Ono, Takeda, Chugai, Nippon Shinyaku, Mochida, MSD, Celgene, Sumitomo Dainippon, and Pfizer. MM, SO, and TTg are employees of Daiichi Sankyo. SS was an employee of Daiichi Sankyo at the time of this study. TT, KM, HO, TS, and RI have no conflicts of interest to declare.
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Supplementary Fig. 1 Kaplan–Meier curve for event-free survival (efficacy analysis set). Patients without a documented best response of CRc were excluded from the analyses. CIs were calculated based on the method proposed by Brookmeyer and Crowley. CI, confidence interval; CRc, composite complete remission; EFS, event-free survival (TIFF 695 kb)
Supplementary Fig. 2 Kaplan–Meier curve for leukemia-free survival (efficacy analysis set). The analyses for LFS were conditional on the patients having a documented best response of CRc. Patients without a documented best response of CRc were excluded from the analyses. CIs were calculated based on the method proposed by Brookmeyer and Crowley. CI, confidence interval; CRc, composite complete remission; NE, not evaluated; LFS, leukemia-free survival (TIFF 662 kb)
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Takahashi, T., Usuki, K., Matsue, K. et al. Efficacy and safety of quizartinib in Japanese patients with FLT3-ITD positive relapsed or refractory acute myeloid leukemia in an open-label, phase 2 study. Int J Hematol 110, 665–674 (2019) doi:10.1007/s12185-019-02727-6
- Acute myeloid leukemia
- FLT3 inhibitor
- FLT3-ITD mutation
- Relapsed or refractory acute myeloid leukemia