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Influx of New Therapies Exciting for Future of AML Treatment

 

Daniel A. Pollyea, MD, MS, University of Colorado School of Medicine, Denver, discusses all the recent drug approvals in acute myeloid leukemia and how they are changing clinical practice.

 

 

Daniel A. Pollyea, MD, MS: The practice of AML is an incredible story right now. It's almost like after years of drought, there's now an embarrassment of riches. We have so many new treatments that are so exciting and work so differently that it's a challenge to think about how to use them, when to use them, what's the right role for each.

When we think about this in general terms there's sort of the targeted therapies and then the sort of non‑targeted therapies.

The targeted therapies are, at least so far, for the most part, approved in the setting of relapse disease, in particular FLT3 inhibitors, the newly approved gilteritinib is approved in the relapse setting. Compared to chemotherapy, it's an oral, a fairly well tolerated treatment that can reliably get patients into remission.

There is a FLT3 inhibitor that's been approved for the last couple years in the upfront setting for patients who are able to receive chemotherapy, and that's midostaurin. I think that's really the standard of care now to give to FLT3 positive AML patients who are eligible for induction chemotherapy.

Other targeted therapies that are now weapons in the arsenal would be those that target IDH2, enasidenib, and IDH1, ivosidenib. Both of these are single agent oral therapies that are approved for patients in the relapse refractory setting. Both of them can have some good success rates and are really viable options and should be considered the standard of care for patients in that situation.

We have an antibody‑based therapy, gemtuzumab ozogamicin, which is an antibody drug conjugate that can seek out and destroy the CD33‑positive blast cells. That's an approved drug.

Many people choose to use that in the untreated setting in a patient who's fit for induction chemotherapy who has good risk disease biology, so typically the core‑binding factor AMLs will receive the 7+3 plus the gemtuzumab.

Then there are a couple other small molecule inhibitors that are important to think about. One is glasdegib. Glasdegib targets smooth end, which is in the hedgehog signaling pathway. This is a drug, that when given with low dose cytarabine to newly diagnosed AML patients who aren't fit for induction chemotherapy, that regimen does better than low dose cytarabine alone. That's an option as well.

Then the other sort of non‑targeted oral therapy is venetoclax, and venetoclax has really been a revolutionary treatment when combined with either low dose cytarabine or more commonly a hypomethylating agent. In the newly diagnosed, unfit for chemotherapy, mostly older population, this regimen has incredibly high response rates, typically north of 70 percent.

These responses have been quite durable, and overall survival is also very, very exciting. This is a very well tolerated regimen for most patients and one that we're very happy to have as an FDA approved therapy.

Then one final one to mention, and that's for patients who are induction‑eligible but have secondary AML or AML that evolved from an antecedent hematologic condition or a treatment‑related AML, they can receive this CPX‑351, which is essentially a 7+3 type regimen, but given in a fixed 5:1 molar ratio.

Patients who received this drug compared to just standard 7+3 had a better survival and higher response rate, so that's also an option.

I think in summary, there are all these new approved therapies that are able to be obtainable outside of the setting of a clinical trial. Lots to learn about the best role for each and how to use them in sequence or together. But that's part of the exciting job that we have going forward in the AML world.

 

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