FLT3 inhibitor-induced neutrophilic dermatosis

Abstract

The FLT3-ITD mutation is associated with poor outcomes in acute myeloid leukemia. Multiple FMS-like tyrosine kinase 3 (FLT3)-inhibitors have been studied in clinical trials. Recently, potent FLT3 inhibition was shown to induce terminal differentiation of FLT3-mutant myeloblasts. In 3 patients who developed characteristic skin nodules on initiation of FLT3-inhibition, we conducted dermatopathologic evaluation of skin samples, as well as FLT3 and NPM1 mutational analysis and fluorescence in situ hybridization. All 3 patients demonstrated characteristically deep dermal and subcutaneous neutrophilic infiltrates without evidence of myeloblasts. Discovery of FLT3-ITD and NPM1 mutations in 2 of the samples, as well as the presence of FLT3-ITD and deletion of 7q in the other, confirmed the ancestry of the differentiated neutrophils as that of the original FLT3-mutant myeloblasts. FLT3 inhibition can lead to clinically distinct dermatoses, which suggests the effect of FLT3 inhibition on myeloid differentiation and a manifestation of a broader "syndrome" associated with this therapy.