Assessing Clinical Trials and First-Line AML Treatment Options


Medical experts elaborate on the AG221-AML-005 and AGILE studies and their results, as well as how we assess first-line treatment response.

Ryan Haumschild, PharmD, MS, MBA: Let's talk about some of the innovative data that we're seeing come up in some of the trials. Dr. McCoy, there's a couple of trials that come to mind for me, the outcomes from AG221 AML and the AGILE study. How does that data fit into or change the treatment landscape that we've talked about thus far?

Cole McCoy, PharmD: Both trials are looking at enasidenib and ivosidenib. They were both originally approved in the relapsed/refractory setting, so they’re looking at these medications for unfit patients. Can we potentially bring them up front in treatment? Looking at the first one, the AG221 AML 005, I was looking at enasidenib plus azacitidine vs azacitidine alone. It was a decently good response; the overall response rate did pretty well. Looking at the AGILE study was just looking at the other one, ivosidenib plus enasidenib or ivosidenib plus azacitidine vs azacitidine alone. Using that up front had good response rates. When looking at the overall picture and where these 2 trials fit in our treatment landscape, I don't think they have truly impacted it yet. In the VIALE-A study that looked at azacitidine plus venetoclax, those patients did well. Patients that are unfit for an induction have a pretty good treatment regimen. There was also a subgroup analysis in that trial that looked at both IDH1 and IDH2 mutations. Those patients did the best out of those groups. [If they have an IDH1 or -2 mutation,] our physicians and hematologists will still treat with azacitidine and venetoclax and then save the enasedinib and ivosedinib in their back pocket in the setting of relapse.

Ryan Haumschild, PharmD, MS, MBA: Dr. McCloskey, as we talk about response, how do you assess response to first-line treatment for AML? Can you talk about how minimal residual disease plays into that decision for you?

James McCloskey, MD: First, bone marrow biopsy is still the standard approach to assessing response to induction. The goal of induction is a remission. There's a variety of types of remission we look at. The first is morphologic remissions. We're looking for clearance of this blast, as Dr. McCoy mentioned, and restoration of normal hematopoiesis. Going deeper, we're looking for cytogenetic remissions. We're looking for resolution in those chromosomal abnormalities and molecular remissions, as well as clearance of those mutations. I often tell patients that MRD is measurable residual disease. It's like an iceberg, right? There's what you see on top of the water, which is what we're looking at under the microscope, and then there's what's below the water and how far down can we measure. This is a very quickly evolving area of AML. There's still some contention there. It is now incorporated in NCCN [National Comprehensive Care Network] guidelines. Whenever we start throwing around measurable residual disease, [we should be] clear about what we're talking about. We struggle in AML because we don't have a great way to track residual disease using immunophenotypes like we do in ALL [acute lymphocytic leukemia] where we can use flow cytometry. There are commercial labs available now that can do that for you. At Hackensack, we have standardized our own flow cytometry in AML, and that's what we use. In the future, we’ll likely be using next generation sequencing to help assess MRD. This is important as we think about transplant because these elderly patients are often receiving reduced-intensity transplants. For a patient with significant MRD and high-risk mutational profiles, the benefit of transplant might be quite limited. There are two reasons MRD is important. Number one, if we have an eligible patient for transplant, is there something we can do to attempt to eradicate that MRD before they go to improve their outcomes? There is not a standardized approach in the setting at this time. There are exciting treatments in development. Any major hematologic malignancy program across the country [will] have trials for your patients who are MRD positive, so reach out to them. It's for going on and assessing the patient's plan for transplant. Besides attempting to get them ready for transplant, should it affect our decision to transplant that patient? That's something that's changing, as we've developed new, effective therapies that change our ability to treat patients in relapse. It's letting us step back as the leukemia doctor and have a conversation with our transplanters. Is it the right thing to transplant this patient with MRD who might be borderline fit for transplant? What other things can we do for them besides the transplant if that transplant is not likely to be successful?

Ryan Haumschild, PharmD, MS, MBA: That was a great overview. You were very thoughtful in the way you talked about MRD, so thank you because it is an emerging area, but it's great to see continued data come out around it.

This transcript has been edited for clarity.

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