Targeting Acute Myeloid Leukemia (AML)

A new molecularly targeted therapeutic for AML and other blood disorders has been approved by the FDA.

The U.S. Food and Drug Administration (FDA) recently approved the first molecularly targeted therapeutic for acute myeloid leukemia (AML), midostaurin (Rydapt). They also approved a companion diagnostic test to identify those patients eligible to receive it – adults newly diagnosed with AML harboring a mutation in the FLT3 gene.

Midostaurin is the first therapeutic approved specifically for treating patients with FLT3 mutation–positive cancer. Midostaurin is intended for use in both the induction phase (chemotherapy given to induce remission) and consolidation phase (chemotherapy given to sustain a remission) of AML treatment, in combination with standard cytarabine and daunorubicin induction chemotherapy and cytarabine consolidation chemotherapy.

Alongside these decisions, the FDA also approved midostaurin for treating adults with certain aggressive forms of a rare disorder known as systemic mastocytosis –aggressive systemic mastocytosis, systemic mastocytosis with associated hematological neoplasm, and mast cell leukemia.

Why approve midostaurin for AML?

AML is the most commonly diagnosed form of leukemia in the United States. In 2017, an estimated 21,380 new cases of AML are expected to be diagnosed. With an overall five-year relative survival rate of 27 percent, AML is the form of leukemia that carries the worst prognosis.

About 25 percent of AML cases are characterized by the presence of mutations in the FLT3 gene. AML patients with this mutation have particularly poor outcomes. Because the FLT3 mutations lead to constitutive FLT3 activation, which promotes survival and proliferation of the leukemia cells, researchers set out to investigate whether targeting FLT3 might provide a new approach to treating patients with FLT3 mutation–positive AML.

Midostaurin targets several related molecules called tyrosine kinase receptors, including FLT3 and KIT. According to the FDA statement, in the phase III clinical trial that led to the approval, patients with FLT3 mutation–positive AML were randomly assigned to receive either midostaurin or placebo during both the induction and consolidation phases of standard treatment.

The results of the trial, which were presented at a conference in December 2015, showed that patients who received midostaurin plus standard induction and consolidation chemotherapy had a 23 percent improvement in overall survival compared with those patients who received placebo.

This article was adapted with permission from a post on the AACR's official blog, CANCER RESEARCH Catalyst.

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