How I treat FLT3-mutated AML

Abstract

FLT3-mutated acute myeloid leukemia (AML), despite not being recognized as a distinct entity in the World Health Organization (WHO) classification system, is readily recognized as a particular challenge by clinical specialists who treat acute leukemia. This is especially true with regards to the patients harboring the most common type of FLT3 mutation, the internal tandem duplication (FLT3-ITD) mutation. Here we present 4 patient cases from our institution and discuss how our management reflects what we have learned about this subtype of the disease. We also reflect on how we anticipate the management might change in the near future, with the emergence of clinically useful tyrosine kinase inhibitors.

Figure 1.

Kaplan-Meier survival curves of relapsed and refractory FLT3-ITD AML patients. (A) Patients relapsing after a first remission duration of 1 to 6 months. These 48 patients were enrolled in the control arm of the Cephalon 204 trial and were treated with MEC, without any FLT3 inhibitor. (B) 25 patients presenting consecutively over a 4-year period to Johns Hopkins who relapsed after a first remission duration of <6 months, or who were refractory to initial induction therapy. They were all treated with intensive, cytarabine-based chemotherapy, but did not receive any FLT3 inhibitors because none were available at the time. All patients in both data sets harbored FLT3-ITD mutations only (no TKD mutations) and the majority were diagnosed between 2005 and 2009.

Figure 2.

Proposed flowchart for the treatment of patients with FLT-3-mutated AML. The final point, maintenance therapy in the post-transplant setting, remains an open question, one it is hoped will be addressed by randomized trials.