Dr. Erba on FLT3 Inhibitors for the Treatment of AML

Harry Erba, MD, PhD, professor of medicine, director, Hematologic Malignancy Program, University of Alabama at Birmingham, discusses the excitement around FLT3 inhibitors for the treatment of acute myeloid leukemia (AML).

It is known that 25-30% of patients with AML with normal karyotype will have activating mutations in FLT3. Though there are a number of drugs that can inhibit FLT3, none are approved by the FDA ​​in this space.

Sorafenib, which is approved for the treatment of hepatocellular carcinoma, renal cell carcinoma, and differentiated thyroid carcinoma, has shown activity in FLT3/ITD-positive AML.

Quizartinib is the furthest along in clinical development and has shown high response rates as monotherapy. Erba says he is concerned about the data because the responses tend to be mostly complete remissions with incomplete blood count recovery, which would be tantamount to clearing leukemia without count recovery. However, Erba says, quizartinib may be an important agent to bridge patients to an allogeneic stem cell transplant, which would be the only curative option for patients with relapsed FLT3/ITD-positive AML.

Patients who respond to quizartinib can develop a D835 mutation, but an agent is being developed that is active against both FLT/ITD and D835 mutations.