Acute Myeloid Leukemia Coverage From Every Angle

Pexidartinib for Relapsed or Refractory FLT3-ITD–Mutant AML

By: Julia Fiederlein
Posted: Tuesday, July 21, 2020

In a phase I/II study, pexidartinib exhibited antileukemic activity in heavily pretreated patients with relapsed or refractory acute myeloid leukemia (AML) who have FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutations, according to Alexander E. Perl, MD, of the University of Pennsylvania, Philadelphia, and colleagues. The results, which were published in Blood Advances, suggested treatment with this type 2 inhibitor of FLT3 was also well tolerated.

“FLT3 tyrosine kinase inhibitors have activity in patients with AML who have FLT3-ITD mutations, but efficacy is limited by resistance-conferring kinase domain mutations,” the investigators explained. “Overall, the safety, tolerability, and clinical activity of pexidartinib in the…population described in this study are supportive of the further development of pexidartinib in AML.”

A total of 90 patients with relapsed or refractory AML who had FLT3-ITD mutations were enrolled. In part 1 of the study, 34 patients were administered oral pexidartinib at daily doses ranging from 800 to 5,000 mg. A recommended phase II dose of 3,000 mg was established and administered to the 56 patients who were enrolled in the part 2 dose-expansion cohort.

The maximum tolerated dose was not reached. Patients who received at least 3,000 mg of pexidartinib seemed to have enough active drug in their trough plasma samples to achieve 95% inhibition of FLT3 phosphorylation in an FLT3-ITD AML cell line. Diarrhea (50%), fatigue (47%), and nausea (46%) were the most commonly reported treatment-emergent adverse events. The overall response and overall composite complete response rates were 21% and 11%, respectively. According to the investigators, 23% of the patients treated with at least 2,000 mg of pexidartinib exhibited a clinical response. The median duration of overall survival was 112 days for the dose-expansion cohort and 265 days for the responders with complete remission with or without recovery of blood cell counts.

Disclosure: For full disclosures of the study authors, visit

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