Acute Myeloid Leukemia: The Path to Personalized Medicine - Episode 17

Insight on Advances in the Treatment of AML

Transcript:Harry Erba, MD, PhD: This has been an incredible discussion. We haven’t been able to have a discussion like this.

Mark J. Levis, MD, PhD: Ever.

Harry Erba, MD, PhD: So I want to thank all of you. But before we end, I’d like to give each of the panelists an opportunity to give us their closing thoughts. And I’ll start at the end of the table with Dr Daver.

Naval G. Daver, MD: Thank you, it was a pleasure. And I think I actually learned a lot of new things, because we weren’t able to attend all of the ASH [American Society of Hematology meeting] sessions. So it was a wonderful discussion. You know our focus is, as we just discussed, a lot on immunotherapies. And I think, as you saw from ASH, a lot of presentations, I think that wave is moving forward. I’m very hopeful that in the near future, the ADCs [antibody-drug conjugate therapies] especially, I think are the ones that will move quickly. The schedule is easier, the management of toxicity is doable even in the community setting, and we’re seeing potency with these agents. So we’re really excited to see a number of these drugs, ImmunoGen, bispecifics, XmAb, AMG 330, moving quickly going into expansions, which most of them are. And the hope is that for VOD [veno-occlusive disease], which we didn’t talk about, we do see VOD with even newer agents. The incidence seems lower. They’re reversible. They’re manageable. But the hope is that it will be something less than we’ve had maybe with Mylotarg, inotuzumab, and we can move to a next generation of ADCs.

I think the other immune arena, the CAR [chimeric antigen receptor] T-cells, the checkpoints, we need to do more work—identify the dosing and identifying if this is something that can be done in big centers. Maybe it’s not going to be something in the community. It may be transplant centers that use this pretransplant, post-transplant, where there’s very potent data that these could be effective.

But the next thing we’re looking at, and I’m sure many investigators here and outside are going to do it: Now that you have these immune therapies, some of which don’t cause myelosuppression, and you have HMA/VEN [hypomethylating agent/venetoclax], what’s the next thing? Of course, it’s combining them, and can you get that 40%, 45% frontline elderly cure rate to 65%, 70%, at which time the immediate question comes up that came to myeloma 10 years ago, do we need 3 plus 7 [regimen]? Can we do this for young patients? And it’s a few years away but that’s where we hope to go.

Harry Erba, MD, PhD: Thank you. Dr Levis?

Mark J. Levis, MD, PhD: Obviously I’m as excited as anybody. We’ve got a lot of new agents in the relapsed setting—palliative reasons, swimming to the Bahamas, etcetera. But honestly, I want to see these agents moved up front in select populations that are genetically defined, and that is where I think we’re really going to move the cure rate for this disease up.

Harry Erba, MD, PhD: Dr Rampal?

Raajit K. Rampal, MD, PhD: I would echo those comments. I think one of the things that we have to do, now that we have all of these agents, is to first pause, right? I think traditionally we’ve seen a patient with AML [acute myeloid leukemia] and we have wanted to move directly to get them down to the 7 and 3 regimen, to get them to transplant. But I think the impetus here is to wait and know what the patient’s actual disease is. What are their cytogenetics? What are their molecular genetics? Because now we have practice changing treatment. If they have MRC [myelodysplasia-related change] findings, then something like liposomal daunorubicin is what we should do because we have a benefit for that. And if they have a FLT3 mutation, we have data for that. So I think the first step is to stop and think about a patient’s individual disease biology before we step into making a treatment decision.

Harry Erba, MD, PhD: I think that’s a critical point. Going way back to the beginning, that hyperleukocytosis retrospective review of 1000 patients, they actually looked at the survival of these patients who received intensive chemotherapy within 2 days, or after, and there was no difference in survival. So we need to control the disease and pause a little bit to get the information that will lead us to making at least a more informed decision with all of these drugs. Dr Perl?

Alexander Perl, MD: I think what’s really exciting is, as you said, this is a rare disease. But we are going to start seeing people come out of the woodwork with this disease because there’s therapy. Because people in the past would say, “Well, I don’t want to go get treated because I don’t think there’s much benefit to that.” And we’re starting to see, a) there’s more options for patients, which means more people can be treated. And when you get these therapies, they give you both more likelihood of benefit and what looks to be more durable benefit. I think that’s a really good thing, because if you look at something like the Swedish [Acute Leukemia] Registry, that said the only thing to predict survival in certain groups of patients was whether they actually got treated or not. We’re going to be treating more patients and I think more people will benefit. And having the tools at our hands to do this work is really nice. So the approvals that we’ve seen in the last 2 years of 8 new drugs really makes our jobs in some ways easier, even though there’s obviously a lot of difficulties in terms of making the best decisions for the best drugs for the right patients.

Harry Erba, MD, PhD: OK. And I’ll end with a concern I have going forward with all of this. There are so many options for patients, and a lot of them are addressing a population that had been underserved, and those are the older, less fit patients, who weren’t part of our clinical trials with intensive chemotherapy. We can’t walk away from the fact that we can cure even older patients with AML. It might be driven by cytogenetic subgroups and molecular subtypes, but there are patients who are older, including older than age 70, who are candidates for intensive therapy. There have been adjuncts to intensive therapy that improve on outcomes. And, let’s not forget, allogeneic transplant is still the most effective antileukemic agent we have because of both chemotherapy and the effect of the marrow. And so, let’s not just rush to give everyone outpatient easy therapy that might continue for a long time. Let’s think about what the goal of therapy truly is.

Mark J. Levis, MD, PhD: That will get you that transplant, less sick.

Harry Erba, MD, PhD: That’s an important point. Thank you, all, for your contributions to this discussion. I’ve really had a great time talking with my colleagues. On behalf of our panel we thank you for joining us, and we hope you found this OncLive Peer Exchange® discussion to be useful and informative.

Transcript edited for clarity.