Expert Perspectives on Current and Emerging Therapies for AML - Episode 14

Treatment Strategies in Patients With Relapsed/Refractory AML

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Centering its discussion on relapsed/refractory acute myeloid leukemia, the panel highlights broader treatment strategies in this setting.

Transcript:

Jorge E. Cortes, MD: Let’s now talk about the patients with refractory or relapsed acute myeloid leukemia and how we handle this approach. We have new treatment options in this setting, but let me ask, Margie, what is your standard approach for these patients? Once you have a patient who didn’t respond or who has relapsed, what do you do?

Margaret T. Kasner, MD: Let me start by saying there is no good standard of care for relapsed/refractory patients. The way I approach them tends to be pretty standard, which is I start with retesting. Patients who are FLT3 positive can relapse as FLT3 negative, and FLT3-negative patients can relapse as FLT3 positive. So the first thing I do is start by gathering the most information that I can because in areas in which there is targeted therapy approved for relapsed/refractory disease, we want to focus on that. My second big standard is clinical trials. Not everyone has access to them, but in general, the outcomes for relapsed/refractory patients is poor, and if there is the opportunity for a trial, I like to look there. What’s become even less standard after the plenary session at this American Society of Hematology meeting is how we get them to transplant. Hetty mentioned that our transplanters don’t even want MRD [minimal residual disease]-positive patients, but the plenary session paper said that maybe you don’t need to treat patients at all if they’re relapsed/refractory, and you can take them straight to transplant. My assessment of that paper is I need the published data because it may not be in line with the way we are practicing in this country. I also don’t know think that I’ve ever met a patient who doesn’t need any therapy for 8 weeks after relapsed/refractory status. I’m not sure what that will mean for our standards. But retesting, thinking about clinical trials, and ultimately getting those patients who can go to transplant to a transplant would be the basis of my standard for relapsed/refractory patients.

Jorge E. Cortes, MD: Absolutely. Hetty touched earlier on the dynamics of fitness, and you touched upon the dynamics of the molecular profile. Both of them must be reassessed regularly as you move on into the therapy. That is very important. One of the first approaches we had approved, a targeted approach, for relapsed/refractory disease was, well a failed attempt for quizartinib, but then a successful attempt with gilteritinib, so FLT3 mutations. How do you incorporate gilteritinib into this algorithm? And do you use it by itself, or do you combine it? Of course, the approval is by itself, but is there any other way of doing this?

Hetty E. Carraway, MD: I’ll take a stab at that. In my patients who are FLT3 mutated with relapse after 7+3 [chemotherapy regimen] and midostaurin or other therapy, I typically lead with single-agent gilteritinib and start with 120 mg for those patients. I have found that, particularly in our older patients, you often need to dose modify because of cytopenias. I’ve typically landed more in an 80-mg-a-day space for them, but I still start with 120 mg because I want to get the best control I can of that FLT3 mutation. For some of my patients in the post-transplant setting, they have been incredibly sensitive to gilteritinib in the relapse post-transplant because their marrow is so sensitive. Nonetheless for those patients, I’ve made them very aplastic, and we’ve been able to get them back on gilteritinib, but more likely in the 40-mg zone. Then in either one of those settings, I also have added venetoclax, knowing that I need to be this chef in the kitchen with figuring out what dose of venetoclax and how to combine that with gilteritinib. I often like to stick with what the recommendations are for patients with relapsed/refractory disease and use gilteritinib only. But for some of those patients with single-agent gilteritinib with progression of their disease, if we don’t have a clinical trial and their disease comes back, a little bit of venetoclax can continue the control, and potentially get some of them back into a setting where we can transplant them. For all of those reasons, I will sometimes move toward combination giltertinib.

Jorge E. Cortes, MD: That’s also important in the context of what Margie was saying, that many of these patients who have FLT3 as they relapse, we often see that the FLT3 clone may not be there anymore or may not be predominant. Often we see emergence of, for example, RAS clones, so that’s relevant.

Transcript edited for clarity.