Quizartinib and omacetaxine mepesuccinate combination therapy in FLT3-ITD AML: a phase II trial - PubMed
6 hours ago
- #FLT3-ITD AML
- #combination therapy
- #resistance mechanisms
- Combined quizartinib and omacetaxine mepesuccinate (QUIZOM) synergistically inhibits FLT3-ITD survival signals like mitochondrial respiration and proteostasis, inducing apoptosis and pro-inflammatory response.
- Phase II trial (NCT03135054) in 40 chemo-refractory/unfit FLT3-ITD AML patients showed an 83% composite complete remission rate, median leukemia-free survival of 10 months, and median overall survival of 12.9 months.
- Higher response rates observed in patients with NPM1 mutations, DNMT3A mutations, and wild-type WT1; single-cell RNA-seq linked pro-inflammatory blast response and CD8+ T cell activation to clinical benefit.
- A resistant leukemic stem cell subpopulation with activated JNK/JUN/HSPA1B axis via PLD1-driven phosphatidylcholine metabolism was identified; PLD1 inhibition remodeled metabolism, induced ferroptosis, and restored QUIZOM sensitivity.