Profile of Quizartinib for the Treatment of Adult Patients with Relapsed/Refractory FLT3-ITD-Positive Acute Myeloid Leukemia: Evidence to Date

• Main Authors: Fletcher L, Joshi SK, Traer E
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-01-01
• Series: Cancer Management and Research
• Subjects: flt3; quizartinib; aml; resistance; clinical trials; quantum
• Online Access: https://www.dovepress.com/profile-of-quizartinib-for-the-treatment-of-adult-patients-with-relaps-peer-reviewed-article-CMAR

Luke Fletcher,1,2 Sunil K Joshi,1–3 Elie Traer1,2 1Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR 97239, USA; 2Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; 3School of Medicine, Oregon Health & Science University, Portland, OR 97239, USACorrespondence: Elie TraerOregon Health & Science University, 3181 SW Sam Jackson Park Road, Mail Code: KR-HEM, Portland, OR 97239, USATel [phone]Fax [phone]Email [e-mail]: Acute myeloid leukemia (AML) is a clonal hematologic neoplasm characterized by rapid, uncontrolled cell growth of immature myeloid cells (blasts). There are numerous genetic abnormalities in AML, many of which are prognostic, but an increasing number are targets for drug therapy. One of the most common genetic abnormalities in AML are activating mutations in the FMS-like tyrosine kinase 3 receptor (FLT3). As a receptor tyrosine kinase, FLT3 was the first targetable genetic abnormality in AML. The first generation of FLT3 inhibitors were broad-spectrum kinase inhibitors that inhibited FLT3 among other proteins. Although clinically active, first-generation FLT3 inhibitors had limited success as single agents. This led to the development of a second generation of more selective FLT3 inhibitors. This review focuses on quizartinib, a potent second-generation FLT3 inhibitor. We discuss the clinical trial development, mechanisms of resistance, and the recent FDA decision to deny approval for quizartinib as a single agent in relapsed/refractory AML.Keywords: FLT3, quizartinib, AML, resistance, clinical trials, QuANTUM