Future Directions in the Management of Acute Myeloid Leukemia

Transcript:

Jorge E. Cortes, MD:Brian, let me ask you about another drug that’s been catching a lot of attention for a while now, magrolimab, this CD47 antibody. You mentioned it earlier in the context of the p53 potential. Tell us more about that and what excites you about this drug.

Brian Andrew Jonas, MD, PhD:Certainly. Just to spend a second on how it works, because I think it’s a mechanism that people don’t know and it works better than CD47 as a “don’t eat me” signal that’s expressed by the leukemia cells and other cancers; it’s also expressed in other diseases too, like MDS [myelodysplastic syndromes]. This protects the cell from the macrophages which go around and surveil and decide if they need to ingest the cell, and so it helps prevent this and the antibody binds to that and disrupts that protective signal so that the cell is then eaten, so to speak. The drug seems to be showing promise in p53-mutated AML [acute myeloid leukemia] and MDS. There was an abstract track looking at its triple combination, and that’s another thing we’ve been discussing today; it also looks exciting. The responses in general, not just p53, look interesting, and when you look at the subset of p53-mutated patients on these combo and new studies, you’re seeing high response rates and, in many cases, durable responses. I think many of us are intrigued by this mechanism and want to see where the phase 3 combination comparative studies go; whether magrolimab can establish itself as a standard of care. I want to point out, because we haven’t talked about it at length, but it also has potential toxicities that we must learn about. One of the biggest ones being anemia because as the red blood cell ages, it increases its expression of CD47. This expected side effect of the medication can lead to hemolytic anemia, so patients will sometimes drop their hemoglobin levels quite significantly after the first dose. People must get used to how to manage this and blood banks need to get a lot of education on how to manage this, especially outside of the academic centers. Regardless, I think it’s an exciting molecule. Now there’s several other CD47 antibodies and [INAUDIBLE] inhibitors that are out there, and I think this is a field that’s going to be excited to see where it goes in the next couple years.

Jorge E. Cortes, MD:Certainly, it’s a very exciting drug. As you mentioned, it comes with some challenges, but as we advance we can learn how to manage these things. There’s many new other agents that we unfortunately don’t have much more time to discuss. There are some bispecific monoclonal antibodies that look very interesting, antibody-drug conjugates, and other targets, SIK [salt-inducible kinase] inhibitors. This is becoming an exciting time in AML, one because the outcomes are changing and treatment is starting to become more effective, less toxic, and more targeted, and that looks very good. Well it’s time to conclude our meeting. Thank you all for this very rich and informative discussion, I learned a lot, like I always do when I hear you. Before we conclude, I’d like to get a few sentences from each of you; final thoughts of unmet needs, future perspectives, or some quick wisdom pearls that you can give us. Let’s start with Dr Carraway, please.

Hetty E. Carraway, MD:I want to thank everybody. I am delighted to share and listen to all of what we just walked through. I would say that the most important things for any patient diagnosed with myeloid disorder is the information that we garner from next-generation sequencing, making sure to look at this data before we embark on therapy, making sure patients have the best therapy in the upfront setting, and putting them in the best place to get and obtain the longest duration of remission possible. Should that patient relapse again, then rechecking for next-generation sequencing so that we can target to the best of our ability and control the disease. As we look forward to the future, we’re going to learn more about the mechanisms of resistance to make sure that we’re combining therapies in a thoughtful and effective way to optimize delivery of drug and minimize toxicities.

Jorge E. Cortes, MD:Thank you. Dr Kasner?

Margaret T. Kasner, MD:I’ll add to that. The abundance of treatment is moving towards targets and that also may mean the outpatient setting. We’re learning a lot about how to manage our patients without watching over them 24 hours a day, which for those of us who’ve been doing this for a long time is hard, but important for our patient’s quality of life, for their caregivers, and for our partners in the community. I look forward to utilizing all of these targeted mechanisms to help our patients live longer and live in their homes for as much as possible.

Jorge E. Cortes, MD:Thank you. Dr Jonas?

Brian Andrew Jonas, MD, PhD:That’s hard to follow. First of all, thank you everyone for allowing me to participate, and Jorge for doing a great job of moderating the session. Being in a group like this with these great luminaries in the field, I’ve learned so much from this. One thing is learning. I think we have a lot to teach our community colleagues about how to partner with academics, who are maybe far from academia, in a way to educate folks about all these new agents. It reminds me when I was a fellow and I was scared by multiple myeloma because there were so many different drugs to learn; and AML is turning into that a little bit. Imagine folks that don’t take care of it as their primary thing, having to wrap their head around all these concepts we’ve discussed today. I want to mention the importance of educating our colleagues and about how to get the right testing and how to treat in optimal ways, and soon to be 2023, and just to point out how exciting the future seems to be for AML.

Jorge E. Cortes, MD:Thank you. I’ll just conclude by agreeing with what you all mentioned. The progress that we’ve seen in the last 5 years or so with a lot of new drugs being approved. For 40 or 50 years, we didn’t have anything new in AML and it has been very exciting, and of course, also very challenging because all of these issues that we discussed; how do you integrate new drugs? How do you combine them, sequence them? Who gets what in what context? Those are going to be some of the big challenges that I see for the future. They become more difficult because we are now talking about a small subset of patients, so doing these studies becomes even more difficult to get that data, but it’s critical because that’s how we’re going to continue advancing and make that next leap into a cure rate that goes well above where it is now. All of you made the pitch for the clinical trials, and we must continue doing that. It becomes even more critical because we want to learn how to use this wealth of new agents that are being developed, but it is also the responsibility of everyone involved in clinical trials to make them accessible to everybody and make them more applicable to the general population, not only to those who can come to our centers. That’s very important. We have seen good progress and the excitement is there, and I think we have the means to make the next leap. Thank you again for your thoughts and discussion. Thank you to our viewing audience for joining us today, we hope you found this OncLive® Peer Exchange discussion to be useful and valuable to the treatment of your patients with acute myeloid leukemia.

Transcript edited for clarity.