DR JOHL: Going back to Suzanne’s case with this patient in the eighties, you mentioned you might consider a hypomethylating agent. The question is, which one? There’s 5-azacitidine. And then we have decitabine, which we have lately had Stanford recommending 10 days of decitabine, daily times 10 days. Or which agent do you use and what doses?

DR STONE: Sure. I think that’s a great question, I think my own view is, I’m looking for randomized prospective data. And although I’m excited about 10-day decitabine, it hasn’t been subjected to a randomized prospective data yet. The decitabine, in a trial that was first-authored by Dr Kantarjian, was compared to low-dose ara-C or supportive care in older adults with AML. And it was slightly better, didn’t quite meet statistical muster.

And then there’s a 7-day azacitidine, which is the standard approach for MDS, that was compared to this conventional care. Unfortunately, not that many of the patients actually got 3 + 7 in the control group. So I tend to use azacitidine for 7 days based on the AML-001 trial. There’s nothing wrong with 5-day decitabine. There’s nothing wrong with 10-day decitabine. It’s more toxic.

The Phase II responses with 10-day decitabine — Cornell, OSU and other institutions — are higher than anything we see with 7 days of aza or a 5-day decitabine, but they haven’t been looked at prospectively yet. There will be a paper at ASH looking at that from the CALGB/Alliance. But anyway, so I use azacitidine for 7 days, to make a long story short.

DR LOVE: Jorge, again, agree, disagree or in between?

DR CORTES: I agree with the basic principle. We’re a little bit biased toward decitabine, but my personal opinion is that there’s probably not much of a difference between decitabine and azacitidine. There’s a little bit of how well you’re used to it. I think the 10-day data is interesting, but right now I consider that as a research tool. We are running a randomized trial between 5 and 10 days. And I think that those will answer the question. But I wouldn’t do it outside of a clinical trial. If I’m going to use decitabine, I’m going to use decitabine 5 days.

DR COLE: So I keep coming back to something that may be even outdated. I’m not that far from my training. I still read a lot of the ASCO book and the ASH-SAP book. And there’s a whole section on adult AML, older AML. And every time I have a new patient, I read it again to refresh my memory on what kinds of statistics I should be quoting these patients.

And there’s a very strong statement that is in the ASH-SAP, that patients who are older with AML are frequently not offered the appropriate therapy, because they are older. And they’re often kind of shuttled into hospice, sometimes without any type of even middle-ground therapy. And there’s a statement that 7 + 3 is still the only thing that has been shown to have a really impactful survival benefit. And so that kind of guided me for many years.

And I also find it interesting to hear you say that all people over the age of 70 at MD Anderson get these hypomethylating agents, because when I was there and covering the ICU as a fellow, the only people that I saw in the hospital — and, of course, these are sick patients in the hospital — had just been induced with 7 + 3. And so I have this interesting feeling of aggressiveness having trained at that place.

DR LOVE: Can I reflect on my vision of this, as I’ve seen this kind of issue played out of age across all cancers with all kinds of people in terms of — I don't know. I was kind of flashing on myeloma, where, kind of, we know transplant is a good thing. And if we think we can get it into a patient — and Lyle, you can tell me whether you view it this way — we try to do it. And it’s just a question of, can we do it?

But I hear something different here, which is, you’re not really offering anything. It’s kind of different than what you read in that guideline. So Rich, what are your thoughts? I mean, I’m not too often that I’ve seen this dynamic in play, where somebody presents a case that they treated, 2 researchers say, “I wouldn’t have done it that way, and this is why,” and then the person goes back and says, “I still would have done the same thing.”

DR STONE: I do want to be a little kinder to you, if that’s the right word. I think what you did was totally reasonable. I mean, I’m just reacting to what I do nowadays. Certainly, the guidelines support what you did.

There’s even a clinical trial that was led by the Eastern Cooperative Oncology Group in older adults that compared clofarabine, which is more intensive than the hypomethylating agents, to 3 + 7. And the trial was stopped before it completed its final accrual, because 3 + 7 was superior in terms of survival. So there’s data on both sides of the issue here. Again, that was for people who were deemed to be 3 + 7 candidates, which is a little different than the AML-001 study I quoted earlier.

So I think you’re well within your — it wasn’t wrong. It’s just that my style of practice has evolved because you can get initial remissions. And it’s often said with the people who wrote the ASH and the ASCO stuff or react to the fact that you don’t get much in leukemia if you don’t get a remission. But that’s really for younger adults. You can actually get benefit in older adults who don’t actually achieve remission, just like you can in MDS, with hypomethylating agents, if people don’t have a complete response. So there’s still potential benefit.

So I think it’s a complicated topic. I mean, I don’t want to say what you did was wrong, but I tend to use 3 + 7 a lot less now in that age group than I did when I was in training, for sure.

DR LOVE: And I would say that, coming out of the original thing we started to do in CME, which is just interviewing people and asking how they take care of patients, moving to all kinds of other formats, that that’s kind of, like, a lot of what we try to do is just say, “Yes. We know there’s a bunch of options, but I’m just kind of curious. What do you do?” The same dynamic when you email people and say, they don’t have the patient in front of them, but they know the situation and they can tell you, “Usually I do X.”

But I’m going to try another experiment in second opinions, because you’ve gotten a second opinion on the initial thing. I want to do a second opinion with you, Jorge, on what she should do now. So, let’s just say she goes, “Okay” — she shoots you an email and says, “Here’s the situation. I decided to do this. Should I keep going with the consolidation or switch to a hypomethylating agent?”

DR CORTES: Obviously, much of that has to do with how the patient is doing tolerating the treatment. I think that I agree with Rich. I mean, we’re talking generalities, but for an individual patient, this obviously was not inappropriate. It was probably a good thing for the patient.

But at some point, you’re going to be limited on how much you can keep going with high-dose ara-C, particularly on an 80-plus-year-old. And so I think that at that point, continuation with a hypomethylating agent could be considered.

Now, of course, we’ve never had the concept of maintenance in AML. We don’t know that it has any value. We’ve used this in post-transplant, hypomethylating agents in high-risk patients. And there’s some suggestion — I would call it “suggestion.” I don’t think there’s definitive data that it improves the probability of a sustained remission. So I would consider it as the continuation of therapy for a patient like this once you get them in remission, because again, I don’t think you’re going to be able to continue with higher doses of ara-C for much longer.

Module 1: Current and future approaches to targeted therapy for acute myeloid leukemia (AML)

Module 2: Other clinical issues in AML management

Module 3: Case discussions