Acute myeloid leukaemia is a quite heterogeneous disease and we’ve learned that the mutational or
pathogenic drivers are quite varied. One of the most common are mutations in the FLT3 tyrosine
kinase. There are generally two types of mutations there – the FLT3 internal tandem duplication ITD
has been associated with a poor prognosis due to high rates of relapse and inferior overall survival.
The TKD mutation is less common and its prognostic impact is less clear. This has been a very
difficult group of patients to treat and we’ve been looking for improvements over the years. We do
have midostaurin in combination with intensive chemotherapy and consolidation.

What was the methodology behind this study?

Adults between the ages of 18 and 75 with newly diagnosed FLT3-ITD positive acute myeloid
leukaemia who were felt to be fit for chemotherapy were analysed for the FLT3-ITD mutation in one of
two central laboratories. During this process they can begin intensive chemotherapy and then on day
8 after the chemotherapy was done they were randomised to receive quizartinib for two weeks as a
single daily dose or placebo. Patients achieving a remission after one or two cycles of induction could
go on to have up to four cycles of high dose cytarabine, again with the same quizartinib versus
placebo randomisation, they could undergo allogeneic transplant and continue that continued
maintenance therapy with quizartinib versus placebo after the transplant. Following consolidation or
transplant up to three years of continued therapy was allowed.

What were the key findings?

The primary endpoint of the study was overall survival and this objective was met. There was an
improvement in the median overall survival: patients receiving quizartinib with intensive induction
consolidation with continued therapy had a median survival of 31.9 months; patients receiving
placebo had a median survival of 15.1 months for a hazard ratio of 0.774 which was statistically
significant.

How could these results affect the future treatment of AML?

These results are quite impactful for the future treatment of patients with AML. This set of patients has
a very poor prognosis. Midostaurin is already approved in patients with acute myeloid leukaemia and
FLT3-ITD or TKD mutations but in this subset of patients with only the ITD mutation, having the worse
prognosis, and in patients up to the age of 75, we saw a survival benefit. The safety profile was
similar to what would be expected with intensive chemotherapy and the known toxicity profile of
quizartinib. So I am hopeful that this drug will become available to my patients, all of our patients, with
FLT3-ITD mutated AML.