Hope for Relapsed AML: Ziftomenib Shows Promise in NPM1-Mutated Leukemia | Eunice Wang, MD | #EHA2025

Hi, my name is Doctor Eunice Wang from the Roswell Park Comprehensive Cancer Center in Buffalo, New York.

I am here at the EHA 2025 meeting and was recently at the ASCO 2025 meeting in Chicago, Illinois. And I'm here to talk to you about some advances in the treatment of AML and some data that's been presented both at ASCO and EHA this year.

So I treat acute myeloid leukemia, which is an aggressive hematologic malignancies found largely in older adults average age 70 years of age. And this tends to be a diagnosis that is imminently life threatening. This is it can be in our older patients a difficult diagnosis to treat.

And I'd like to emphasize is now in this day and age, it's important when patients are confronted with the diagnosis of AML that they undergo the appropriate diagnostic testing. And that includes right now, in this day and age, testing for certain mutations and genetic abnormalities with this disease.

Why is that important? It's important a diagnosis and is recurrent recontact at the time of relapse, because it can influence your treatment modalities and the treatment options available to you, as well as affect your overall outcomes.

So there is a mutation, a nuclear phosphide one or MMP one that is diagnosed and up to one third of newly diagnosed patients, and can also be present in most cases also at the time of disease recurrence.

So at the ASCO 2025 meeting, I presented the results of the KOMET-001 study. The phase 1b, phase two study that looked at the treatment of patients with relapsed refractory and then P1 mutant AML.

These patients who have failed at least anywhere between 1 to 7 prior lines of therapy, median of two, have a dreadful outcome with the historic response rate to salvage chemotherapy of only 12%.

In this trial, we were looking at whether treatment with the novel drugs, ziftomenib, which is a class of agents called menin inhibitors, can perform better in this relapsed refractory patient population than standard chemotherapy, which, as I mentioned, has a response rate of only 12% and a survival of only a few months in patients.

So in the KOMET-001 this phase 1b and phase two study, there was a 112 patients that I presented. And using ziftomenib, which is a daily oral agent at 600mg once a day, we were able to show that about 35% of patients had clinical benefit from taking a pill once a day.

A targeted therapy for NF1 mutant relapsed refractory disease. What does this mean? This means that up to a third of patients had clinical benefit, 2,325% had a complete remission, meaning their disease disappeared in their bone marrow under 5%.

And in a majority of these patients, two thirds of these patients, we couldn't even detect the disease that went into response using our most sensitive minimal residual testing.

And patients that got this treatment stayed had a duration of response about 3.7 months. And responding patients, patients that had any clinical benefit with the drug survived a median of 16.4 months.

That's a huge amount of time for a disease for which we only really have, very limited therapies. Patients who didn't respond had the standard survival of only 3.5 months.

So we think that adding this oral drug was actually really well tolerated. There wasn't very many, side effects, including low blood counts, which are found in only about 20% of patients.

We see this unique differentiation syndrome, which just something that you just have to look out for weight gain, fluid retention, etc. and only about 3% of patients discontinued the drug because of side effects.

We think this sounds to me like a good therapy, and this drug is currently being reviewed by the FDA and a priority review for a potential FDA approval as early as the end of November in 2025.

We also saw here at, EHA that there is very promising data in moving these types of agents is menin inhibitors into the upfront setting, as well as the relapsed refractory setting in combination with intensive and less intensive chemotherapy.

There are phase three trials, including trials looking at ziftomenib and moving that up to upfront therapy of AML patients. And we saw continuing data with other targeted therapies targeting other abnormalities.

Flip three mutations, IDH1 and IDH2 mutations.

So, just wanted to remind our listeners that and patients that it is important to seek the most expert advice for the treatment of your acute myeloid leukemia, whether that means going to a major medical center, asking for referrals.

Clinical trials are always a priority for this particular patient type, and getting the molecular testing done by your physician or at that referral site to see whether any of these targeted therapies like ziftomenib might be something that you would be eligible, can drastically transform.

You know, your outcomes, your survival duration, the side effects that you're having, and just give you more options for acute myeloid leukemia.

Thanks so much for your attention. I'm grateful for the opportunity to speak to you today.