Frontline Treatment in Patients With IDH-Mutated AML Unfit for Intensive Chemotherapy

In the setting of IDH-mutated AML, panelists consider optimal treatment options in patients unfit for intensive chemotherapy.


Jorge E. Cortes, MD: Hetty, we talked earlier about IDH inhibitors. For unfit patients, there are prospective data. There is an approval, at least for ivosidenib. How do you incorporate that in the frontline setting? What do you do for patients with IDH1-mutated AML [acute myeloid leukemia]? We know that azacitidine-venetoclax works well, but these are approved drugs and they’re targeted. Which of the 2 do you use? Do you use ivosidenib alone or ivosidenib plus azacitidine? Tell us about your thought process.

Hetty E. Carraway, MD:For many of our patients, we aren’t getting that IDH mutation back soon enough. If we’re going to use an azacitidine-venetoclax approach, we’ll launch into that. Often that’s happening in the region before those patients even come to us, and that’s where some of the rub is. There’s a patient in your hands at that moment, so you can intervene and leave with something like azacitidine-ivosidenib in the up-front setting. All of us in the leukemia community, whether it’s at large academic centers or in the region, know that we can proceed with azacitidine-venetoclax and then get the next-generation sequencing back for some of those folks. I don’t think it’s wrong to lead with azacitidine-ivosidenib for those IDH1-positive patients, but for some we lead with azacitidine-venetoclax and save the IDH inhibitor for later.

We talked about how, if these patients are fit enough, we probably do that knowing that azacitidine-venetoclax isn’t chemotherapy-lite. It can be challenging for our patients to endure the pancytopenia that happens. For some of those patients, if we’re truly worried about their ability to tolerate combination azacitidine-venetoclax, I have no problem leading with an IDH inhibitor and seeing how they do. If we can get them to be less symptomatic from their leukemia and to have more reconstitution of their marrow, then in the normal sense they’ll recover and move to other therapy in the future, where you add azacytidine. I often tailor this, depending on the fitness of the patient and what kind of support they have in the outpatient setting, [to help them] get through this.

Jorge E. Cortes, MD: It’s become more of a practical thing than academic or scientific. Realistically, most patients who we’ve already seen started, or because of the wait time, need to go ahead. Aside from issues of the weight and availability of the test, what about IDH2 and enasidenib? Does that have a role in the front line?

Hetty E. Carraway, MD:In the up-front setting, I’ll still lead with azacitidine-venetoclax for most patients and reserve the IDH inhibitor for later if they’re not able to tolerate therapy, recognizing that they may be less likely to respond to those agents after they’ve had nice responses to azacitidine-venetoclax. It depends on their goals of care. If they’re patients who are going to transplant, our transplant doctors get a little nervous with single-agent ivosidenib or azacitidine. I’m not saying I’m uncomfortable with it, but if I’m trying to persuade my transplant doctor to transplant 1 of these patients, we’re influenced by what they’re comfortable with in terms of moving to transplant. We must push back a little regarding that, but if patients are able to tolerate combination therapy, that’s something that we lead with.

Transcript edited for clarity.

Related Videos
Matthew Matasar, MD, chief, Division of Blood Disorders, Rutgers Cancer Institute; professor, medicine, Rutgers Robert Wood Johnson Medical School
Sattva S. Neelapu, MD
Sattva S. Neelapu, MD
Julie M. Vose, MD, MBA
Lakshmi Nayak, MD
John Burke, MD
Timothy Hughes, MD, MBBS, FRACP, FRCPA
Ben Levy, MD, and Yan Leyfman, MD
BTK Inhibitors in CLL : Second Generation Drugs and Beyond
Video 14 - "Key Takeaways in HER2-Mutated NSCLC"