Treating Relapsed/Refractory AML


Drs McCoy and McCloskey discuss relapsed/refractory AML, including treatment goals and options.

Ryan Haumschild, PharmD, MS, MBA: Dr. McCoy, what are some of the treatment options for patients with relapsed/refractory AML [acute myeloid leukemia]? Can you give us an overview of those treatment options that we've discussed so far?

Cole McCoy, PharmD: This is an unfortunate situation, and patients that do have [a] relapse might have to go back to the beginning and see what their fitness is. If they're fit enough for an induction at that time, they may go through a reinduction. There's not a specific regimen that is a standard of care at the moment. There are several out there, and a lot of them are very institution specific. For example, there's CLAG-M. We always give these fancy abbreviations to these regimens, but that's cladribine, high-dose cytarabine, and mitoxantrone. Other institutions may, for example, use FLAG-Ida, which is just fludarabine, hydro cytarabine, and then idarubicin. MEC is another one that some institutions use, but those tend to be more intense than what they originally got in a 7 plus 3. If patients are fit enough, they may get this intense reinduction.

We talked about monitoring those [targeted therapies] at the beginning. At the relapse stage, we should be sending out to see if those are there, still there, or [if] they picked up a new mutation. We talked about some medications that are approved in that relapsed/refractory setting if they have an IDH mutation—IDH1, ivosidenib, and IDH2, enasidenib. They could take an oral medication if they have a specific mutation at home. The other that's approved in the relapsed/refractory setting is gilteritinib That's a FLT3 inhibitor in that setting that was compared against other salvage chemotherapy. It had improved outcomes compared with traditional chemotherapy. You have to decide if they're fit enough for another induction where they get that CLAG-M or FLAG-Ida. If they have a targeted mutation, you have some other options there as well.

Ryan Haumschild, PharmD, MS, MBA: That was a great overview of the different therapies. I want to pivot to Dr. McCloskey. We heard about these new therapies. What are some of the goals of treatment that you're looking for with patients with relapsed/refractory AML? Do you perform any cytogenetic testing in the relapsed setting?

James McCloskey, MD: Absolutely. It is crucial to repeat your cytogenetic and molecular testing at relapse. The disease at relapse could look very different than it did at initial diagnosis. It's important to confirm if there were targetable mutations at diagnosis that are still there, or have there been new targetable lesions that have emerged that were not there initially and were missed? Both can happen frequently. In terms of goals, this is important because I the first thing we're entertaining is [whether] this patient is a good fit/candidate for a transplant. If they were a favorable risk patient who didn't go to transplant in CR1, are they a candidate to go now? If we get a CR2, what was the length of CR1 in that case? I think that Dr. McCoy highlighted several well-understood salvage regimens that might be more beneficial in a patient who's been in remission for 18 months compared with someone who was just on or is in the middle of consolidation. Along with that, we've talked about patient goals, understanding that for a patient with relapsed or refractory AML, their prognosis is very poor. It is important that we understand their quality of life issues and what's important to them if we're not able to offer them treatments that are going to be curative or result in long-term disease control.

This transcript has been edited for clarity.

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