In this installment of the “How I treat …” series in Blood, the authors present four clinical case studies of patients with FLT3-mutated acute myeloid leukemia (AML) to illustrate their strategies to treat both newly diagnosed patients and those with relapsed or refractory disease.
The authors describe the biology of FLT3-mutated AML, focusing on the common internal tandem duplication (FLT3-ITD) mutation, and illustrate how the mutation’s proliferation pathways make it especially vulnerable to disruption by FLT3 tyrosine kinase inhibitors (TKIs). They focus on the TKIs now being investigated in phase III trials: midostaurin, sorafenib, quizartinib, gilteritinib and crenolanib.
They describe the evidence supporting the use of a FLT3 TKI after failed standard therapy to stabilize the disease sufficiently to permit allogeneic transplantation. Regarding the use of FLT3 TKIs as post-transplant maintenance therapy, the authors note that while they appear to be generally safe, there have been no randomized trials establishing their benefit.
The authors therefore recommend enrolling eligible patients in an upcoming Blood and Marrow Transplant Clinical Trials Network (BMT CTN) clinical trial (BMT CTN 1506), a multi-center randomized double-blind, placebo-controlled trial of a FLT3 TKI (gilteritinib) as post-transplant maintenance.