Treating Newly Diagnosed Acute Myeloid Leukemia

EP: 1.The Role of Molecular Testing in Diagnosing Acute Myeloid Leukemia

EP: 2.When to Perform Molecular Testing in Relapsed AML

EP: 3.Barriers to Molecular Testing in AML

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EP: 4.Treating Newly Diagnosed Acute Myeloid Leukemia

EP: 5.Treatment Options for a Young, Fit Patient Newly Diagnosed with AML

EP: 6.First-Line Treatment Options for NPM1-mutant AML

EP: 7.First-Line Treatment Options for AML With KMT2a Rearrangements

EP: 8.The Potential Role of Menin Inhibitors in the Front-Line Treatment of AML

EP: 9.Exploring Potential Combination Treatments for AML

EP: 10.Menin Inhibitors in the Second-Line Treatment of AML

EP: 11.The Role of Menin Inhibitors in the AML Treatment Armamentarium

EP: 12.Determining Which Patients Will Benefit the Most From Menin Inhibitor Treatment

EP: 13.The AML Treatment Horizon

EP: 14.Menin Inhibitors in Acute Myeloid Leukemia: An Overview of “Encouraging” Early Data

Transcript:

Naval G. Daver, MD: I’m going to now move to treatment of newly diagnosed AML. We started already getting into this of course because it’s quite linked to the molecular cytogenetics. But I’ll turn it here to Dr Pollyea to give his thoughts on treatment options. So first maybe to start with, what we can call provocative, but I don’t think it’s provocative. I think most of us are getting to that agreement of how do you select patients for intensive chemotherapy? Do we like these terminologies of fit, unfit? Do we like to say suitable, unsuitable? And what really goes into your thought process when you’re saying I’m going to give this person intensive chemo[therapy] or I’m going to go for HMA-based? It may be HMA-VEN. It may be a triplet. It may be a new [combination] HMA-IDH. So, Dan, how do you make that decision for a patient sitting in front of you?

Daniel Pollyea, MD, MS: I really would like us to get away from the sort of terminology of fit vs unfit, because it carries with it a lot of baggage. And it had some relevance from a previous era in which we no longer live, and so there is quite a bit of confusion around it. I think fitness for intensive induction chemotherapy was always controversial. There were attempts to make objective criteria around this. I think experienced leukemia doctors were very subjective about it. And you know it was age, it was comorbidities, it was experience. And those are the things that went into making this decision. Now fitness for intensive induction chemotherapy in an era in which that was the only treatment that we could provide, that had any chance of long-term, good outcomes was a really important decision.

It had a huge amount of weight to it. Fortunately, we are now in a different era where we have other therapies that are active against this disease. And so, continuing to assess fitness for intensive induction chemotherapy as if that is the only appropriate treatment option I think is problematic. And so, what I would like the field to do and what I’ve been trying to do is to apply intensive induction chemotherapy in the patients for whom it is likely to really work. And there are patients for whom intensive induction chemotherapy can be curative. And so, continuing to advocate for this and apply it in those situations is important. And even stretching the former definition of fitness in a situation in which a patient could be cured because of their disease biology—favorable-risk disease biology is what I’m talking about here—that’s a patient that even if they’re marginally fit … for intensive chemotherapy, they should probably get it. We should take that risk because cure is on the table.

But outside of those situations, I think we really need to think broadly about the tools at our disposal and how we can match up the best possible therapy for our individual patient. And that’s not just the up-front treatment strategy. That’s also thinking down the road to how we’re going to cure a patient. And sometimes a less intensive strategy that’s safer and may be more reliable based on patient disease biology, that allows a patient to get into a remission and then allows them to proceed to a transplant [that] can be curative, is something that we need to really think about and prioritize for our patients even at the time of diagnosis. So, it’s a long answer. I hope I answered it a bit. But … we need to … think about all the treatments that are at our disposal and apply the best one for the patient regardless of whether a patient is likely to survive intensive chemotherapy, which is really what we’re talking about when we talk about fitness. We’re not talking about how likely they are to respond or do well or live a long time. It’s just, can they survive it? That seems like a low bar, and I think we’re in a place now where we do better.

Harry P. Erba, MD, PhD: You used the term that we used, that Mikkael A. Sekeres[, MD,] used in an American Society of Hematology (ASH) guidelines paper: appropriateness. Is it appropriate to give them intensive or less intensive chemotherapy? I do things the same way as you do, and I think what’s interesting for our listeners to realize is Gail Roboz[, MD,] likes to call this the no-data zone. We don’t have these randomized trials in fit patients of intensive vs less intensive therapy. The MyeloMATCH program sponsored by the National Cancer Institute will launch this year to answer some of those questions. But you’re right, Dan, a lot of us think that we’ve already had those questions answered, and especially in patients with poor-risk disease, although we don’t have phase 3 data yet.

Daniel Pollyea, MD, MS: Your efforts and others’ in the field to get that data, to put those trials out there, extraordinary efforts. Hugely important so we can take the guesswork out of this. And for folks who are participating in this, it’s important to help us get better by referring patients for clinical trials like these.

Naval G. Daver, MD:Yes, and just to highlight … I agree totally. I think the fitness concept, and just to give a background on how that came into being. This was really based on patients who could get only 1 of 2 options, either intensive chemotherapy or HMA. And so, we would push those patients to get intensive chemo[therapy] because the HMA response rate was 20%, and intensive chemo[therapy] was 80%, 70% to 80%. So, this was really can we get this patient through intensive chemo[therapy], because that’s the only thing that has a good chance of improving long-term outcome, response, and survival. But now with the advent of HMA+VEN and other combinations, the response rates are quite similar. And so, now we can change that thought process and say what is the best treatment? I would even go far as to say who really benefits and needs intensive chemo[therapy]? I think the default should be, can we avoid intensive chemo[therapy] for those patients who may not need it? I think we’re moving into that direction. Randomized studies are starting. Amir Fathi[, MD,] has one ongoing. There’s one in Europe with Charlie Craddock[, CBE,] and the group. The MyeloMATCH is doing it, so I think we’ll learn more going forward.

Transcript is edited for clarity and readability.