Ryan Haumschild, PharmD, MS, MBA: Let’s talk about some of the innovative data that we’re seeing popping up in some of the trials. dr. McCoy, there are a number of studies that come to mind, the results of AG221 AML and the AGILE study. How does that data fit into or change the treatment landscape we’ve talked about thus far?
Cole McCoy, Pharm D: Both studies look at enasidenib and ivosidenib. They were both originally approved in the relapsed/refractory setting, so they’re looking at these drugs for inappropriate patients. Can we possibly bring them to the front of the treatment? When I looked at the first, the AG221 AML 005, I was looking at enasidenib plus azacitidine versus azacitidine alone. It was a pretty good response; the overall response fared quite well. When we looked at the AGILE study, we only looked at the other, ivosidenib plus enasidenib or ivosidenib plus azacitidine versus azacitidine alone. Using that upfront, response rates were good. When I look at the overall picture and where these 2 studies fit into our treatment landscape, I don’t think they have had a real impact on it yet. In the VIALE-A study looking at azacitidine plus venetoclax, those patients did well. Patients unsuitable for induction have a reasonably 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 doctors and hematologists will still treat with azacitidine and venetoclax and then keep the enasedinib and ivosedinib in their back pocket in case of a relapse.
Ryan Haumschild, PharmD, MS, MBA: dr. McCloskey, speaking of response, how do you rate response to first-line treatment for AML? Can you tell me how minimal residual disease plays a role in that decision for you?
James McCloskey, MD: First, bone marrow biopsy is still the standard approach for assessing response to induction. The goal of induction is a remission. There are a variety of types of remission that we look at. The first is morphological remissions. We seek clarification of this explosion, as Dr. McCoy said, and recovery from normal hematopoiesis. If we go deeper, we look for cytogenetic remissions. We are looking for a solution in those chromosomal aberrations and molecular remissions, as well as elimination of those mutations. I often tell patients that MRD is a measurable residual disease. It’s like an iceberg, right? There’s what you see on top of the water, that’s what we look at under the microscope, and then there’s what’s under the water and how far down we can measure. This is a very rapidly evolving area of AML. There is still some twist there. It is now included in NCCN [National Comprehensive Care Network] guidelines. Whenever we start spreading measurable residual disease, [we should be] clear what we are talking about. We struggle with AML because we don’t have a great way to detect residual disease using immunophenotypes like we do in ALL [acute lymphocytic leukemia] where we can use flow cytometry. There are now commercial labs available that can do that for you. At Hackensack we have standardized our own flow cytometry in AML, which is what we use. In the future, we will likely use next-generation sequencing to help assess MRD. This is important when we think about transplantation, because these elderly patients often undergo reduced-intensity transplants. For a patient with significant MRD and high-risk mutational profiles, the benefit of transplantation may be quite limited. There are two reasons why MRD is important. First, if we have a patient who is eligible for a transplant, is there anything we can do to try and eradicate those MRDs before they improve their outcomes? There is currently no standardized approach in the setting. Exciting treatments are in development. Every Major Hematology Malignancy Program Across the Country [will] have studies for your patients who are MRD positive, so get in touch with them. It is to go ahead and review the patient’s transplant plan. Besides trying to get them ready for transplant, should it influence our decision to transplant that patient? That’s something that’s changing, as we’ve developed new, effective therapies that are changing our ability to treat patients with relapse. It makes us step back as leukemia doctors and engage in conversation with our transplanters. Is it the right choice to transplant this patient with MRD who may be eligible for transplant? What other things can we do for them besides the transplant if that transplant is unlikely to succeed?
Ryan Haumschild, PharmD, MS, MBA: That was a nice overview. You were very thoughtful in the way you talked about MRD, so thank you because it’s an emerging area, but it’s great to see more and more data coming out about it.
This transcript has been edited for clarity.
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