Novel agents changing treatment algorithm in AML

Dr. Stone also said CPX-351 may be added to induction for fit older patients with secondary AML.

Enasidenib and ivosidenib

In relapsed AML, the treatment approach is to induce a second complete remission and then proceed to allogeneic stem cell transplant.

Traditionally, FLAG-IDA (fludarabine, cytarabine, idarubicin, and G-CSF) and MEC (mitoxantrone, etoposide, and cytarabine) have been used as salvage, and another course of 7+3 is an option if the patient has been disease-free for over a year.

Now, however, enasidenib and ivosidenib may be an option for IDH2- and IDH1-mutated patients, respectively.

The FDA approved enasidenib in 2017 to treat adults with relapsed or refractory AML and an IDH2 mutation, as detected by an FDA-approved test.

Ivosidenib was approved by the FDA this year to treat adults with relapsed or refractory AML who have an IDH1 mutation, as detected by an FDA-approved test.

New approaches on the horizon

Dr. Stone noted that gilteritinib and quizartinib are currently in development for FLT3-mutated patients, and he anticipates these therapies will be approved by the FDA in 2019.

Dr. Stone also touched on other new approaches under investigation, such as hedgehog pathway inhibition, dysregulation of the spliceosome complex, inhibiting MDM2, and strengthening the immune system.

However, he believes the most important is BCL-2 inhibition with venetoclax.

Venetoclax combined with a hypomethylator (azacitidine or decitabine) produced a response rate of 75% with azacitidine, double what one would expect with azacitidine or decitabine alone, Dr. Stone noted.

And venetoclax with low-dose cytarabine may enable elderly good-risk patients to avoid 7+3.

Dr. Stone’s presentation also covered genes commonly mutated in AML, the increasing scrutiny of complete remission, and minimal residual disease assessment. An account of this part of the presentation can be found here: “Current management of AML patients.”