Quizartinib Resistance Mutations and Treatment Outcomes in Relapsed or Refractory FLT3-ITD-Positive AML

Area of Science:

• Hematology
• Oncology
• Pharmacology

Background:

• Quizartinib is a targeted therapy for FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (FLT3-ITD)-positive acute myeloid leukemia (AML).
• Understanding resistance mechanisms is crucial for improving treatment strategies in relapsed or refractory FLT3-ITD-positive AML.

Purpose of the Study:

• To evaluate quizartinib resistance mechanisms in patients with relapsed or refractory FLT3-ITD-positive AML.
• To assess the efficacy and safety of quizartinib in this patient population.

Main Methods:

• A multicenter, single-arm study conducted in Japan enrolled 18 patients.
• Fifteen patients received oral quizartinib (up to 53 mg daily) for up to 12 cycles.
• Resistance mutations, composite complete remission (CRc), overall response rate (ORR), overall survival (OS), and adverse events (AEs) were evaluated.

Main Results:

• Acquired mutations (NF1, CSF3R, NRAS, FLT3) were detected in 4 of 7 evaluable patients; FLT3-ITD loss occurred in 2.
• The CRc rate was 66.7%, ORR was 73.3%, and median OS was 13.6 months among 15 treated patients.
• Grade ≥3 non-hematologic AEs and grade 1 QT prolongation were observed in 20.0% of patients.

Conclusions:

• This study provides insights into quizartinib resistance mechanisms, including acquired mutations and FLT3-ITD loss.
• Quizartinib demonstrated notable efficacy and a manageable safety profile in relapsed/refractory FLT3-ITD-positive AML patients.