The venetoclax+HMA strategy is also a notable salvage regimen that achieves good clinical outcomes in the treatment of relapsed or refractory (R/R) AML. However, in our clinical practice, we found that disease progressed rapidly even after venetoclax+azacitidine (AZA) therapy in two relapsed t(8;21) AML patients with KIT mutations. We report for the first time the therapeutic potential of venetoclax+midostaurin as a new combination therapy for relapsed t(8;21) AMLs with KIT mutations showing resistance to venetoclax+AZA therapy.