Venetoclax-based salvage therapy in patients with relapsed/refractory acute myeloid leukemia previously treated with FLT3 or IDH1/2 inhibitors
Jan Philipp Bewersdorf, Rory M. Shallis, Andriy Derkach, Aaron D. Goldberg, Anthony S. Stein, Eytan M. Stein, Guido Marcucci, Amer M. Zeidan, Shai Shimony, Daniel J. DeAngelo, Richard M. Stone, Ibrahim Aldoss, Brian Ball, Maximilian Stahl
Abstract
FLT3, IDH1 and IDH2 inhibitors as well as venetoclax in combination with hypomethylating agents or low-dose cytarabine have expanded treatment options for patients with acute myeloid leukemia (AML). However, little data exist on the efficacy of venetoclax-based therapies in AML patients previously treated with FLT3 or IDH1/2 inhibitors. In this multicenter, retrospective cohort study, we included 44 patients who received venetoclax-based therapy after FLT3, IDH1 or IDH2 inhibitors. The overall response rate (ORR; composite of complete remission [CR]/CR with incomplete count recovery, partial remission, and morphologic leukemia free state) was 56.8% (18.2% CR) and a median overall survival of 9.2 months. While 6 out of 7 patients with IDH1 mutations who had previously been treated with ivosidenib responded to venetoclax-based therapy, FLT3-ITD mutations were associated with a lower response rate. Our data suggest that venetoclax can be an effective salvage therapy in patients previously treated with IDH1/2 or FLT3 inhibitors.