Combination of BTK Inhibitor Overcomes Drug-resistance in Refractory/Relapsed FLT3 Mutant AML

Overview

Clinical efficacy of FLT3 inhibitors combining with chemotherapy is usually transient and followed by emergence of drug-resistance in FLT3-ITD mutant AML. BTK is reported to be a therapeutic target in this subtype leukemia. Our previous study showed inhibition of BTK onvercome drug-resistance to FLT3 inhibitors/chemotherapy in refractory/relapsed FLT3 mutant AML. In this prospective randomized controlled study, the efficacy and safety of combination of BTK inhibitor with chemotherapy with/without FLT3 inhibitor in refractory/relapsed FLT3 mutant AML are evaluated.

Clinical efficacy of FLT3 inhibitors combining with chemotherapy is usually transient and followed by emergence of drug-resistance in FLT3-ITD mutant acute myeloid leukemia (AML). How to overcome the resistance to FLT3 inhibitors or chemotherapy needs further study. Bruton's tyrosine kinase (BTK) is reported to be a therapeutic target in this subtype leukemia. Our previous study showed inhibition of BTK onvercome drug-resistance to FLT3 inhibitors/chemotherapy in refractory/relapsed FLT3 mutant AML. In this prospective randomized controlled study, we are going to inhibit BTK with BTK inhibitor ibrutinib in the patients with refractory/relapsed FLT3 mutant AML, and then test the enhancing effect and safety of combination of ibrutinib with chemotherapy with/without FLT3 inhibitor, to make sure inhibition of BTK overcomes drug-resistance in FLT3 mutation AML.

Conditions