Manoj Kumbhare, Siddhi Chandak*, Bhagwan Ide, Aishwarya Dukare, Sakshi Velhal, Harshali Gode, Nishant Pagere,

Arshad Shaikh

* Address    for  Correspondence:

Siddhi M. Chandak,

Department of Pharmaceutical Chemistry, SMBT College of

Pharmacy, Dhamangaon, Nashik – 422403, Affiliated to Savitribai

Phule Pune University, India

Email: siddhimchandak@gmail.com

ORCID ID: 0009-0006-7860-2388

Abstract

Acute Myeloid leukemia (AML) is a genetically heterogeneous hematologic malignancy that disproportionately affects older individuals. Among the various genetic alterations, FLT3 internal tendem duplication (FLT3-ITD) mutations are present in approximately 20-30% of patients and are linked to rapid disease progression and frequent relapses. This review evaluates the role of quizartinib, a second-generation, highly selective FLT3 inhibitor, as a targeted therapeutic option for relapsed or refractory AML. Preclinical studies have demonstrated that quizartinib offers potent inhibition of FLT3 signaling, favorable pharmacokinetic properties, and high bioavailability. Early-phase clinical trials reported promising remission rates in patients harboring FLT3-ITD mutations, while phase III studies further substantiated its efficacy by showing improved overall survival when used alone or alongside standard chemotherapy. Despite these advances, quizartinib’s clinical use is limited by challenges such as acquired resistance, off-target effects—including QT interval prolongation—and complex drug-drug interactions. Ongoing research is focused on elucidating resistance mechanisms and developing effective combination regimens to optimize its therapeutic potential. Overall, quizartinib represents a significant breakthrough in precision medicine for AML, offering a promising avenue to improve patient outcomes in this challenging disease.

Keywords  FLT3 Mutations, Acute Myeloid Leukemia (AML), Quizartinib, FLT3 Inhibitor, Relapsed/Refractory AML, FLT3-ITD Mutations

PDF  Targeting FLT3 Mutations in Acute Myeloid Leukemia: The Role of Quizartinib in Precision Medicine.pdf