Can gilteritinib cure AML?

The ADMIRAL trial showed an improvement
in the median survival of patients

treated with gilteritinib from about 5 to 6 months

to nine months.

Now,

very few
patients were still receiving gilteritinib

after two years, and that shouldn't be unexpected
since FLT3 mutations

especially the IDT
mutation, is a late event in leukemogenesis.

So I think it would be unlikely
that a single agent such as gilteritinib

would be effective as a more prolonged
maintenance therapy in patients.

I think
it's highly unlikely that any FLT3 inhibitor

as a single agent would be curative for acute
myeloid leukemia, as we know.

This is a very heterogeneous disease.

The median number of mutations in patients is four

and FLT3 mutations, especially the ITD are late
events in leukemogenesis.

So by just targeting FLT3 with an inhibitor,
I think it's highly unlikely

that we'll get prolonged remissions
with single agent therapy.

And so we really do need to stress
and focus on combinations with chemotherapies

either intensive, such as 7+3 and high dose
cytarabine or less intensive therapies

in order to see a benefit of FLT3 inhibition
or in the future immunotherapies

as well in combination with FLT3 inhibitors
such as gilteritinib

Resistance can occur

with any FLT3 inhibitor that we use in the clinic.

In terms of gilteritinib,
we do see resistance develop

now, since gilteritinib is a type one inhibitor

and it inhibits both the FLT3 ITD
and the TKD mutation, when patients progress

on gilteritinib, they typically do not have a FLT3
ITD or TKD mutation.

However, other mutations develop,
and the most commonly identified mutation

in those patients are mutations in RAS.