DR COLE: So this is a really nice guy, of course. So he was referred to me with pretty mild-ish cytopenias. His white count was 2 x 10³/mcL. His platelets were 42 x 10³/mcL. He had an elevated MCV. His PCP, he just called me and said, “Hey. I don’t like the way this looks. Can you see him quickly?”

So I got him in. We did a bone marrow, and he came back with AML, 47% blasts, had a lot of megakaryocytic dysplasia. And so they had commented that they thought he probably had some preceding myelodysplastic syndrome. He had a 1;16 translocation. His FLT3 was negative. The rest of his panel was also negative, but he had an abnormal monosomy 7.

And for 83, he was very fit. He was playing 18 holes of golf the day before he came into my office, had some mild cardiac issues, hypertension, a little arrhythmia in the past.

But once his bone marrow came back as AML, we had a pretty heavy conversation about whether to do full-on induction or something a little bit lighter. And he just was all in. And so we decided to do 7 + 3, and he actually did quite well, went through the induction with no problems. His first bone marrow, he was in remission at day 14 and continued to be in remission at day 28. And now he is currently in the midst of receiving consolidation.

DR LOVE: And I’ve got to ask, is he the oldest patient where you’ve used 7 + 3?

DR COLE: I think I had an 86-year-old when I was first coming out.

DR LOVE: Interesting. Rich, what’s your oldest patient? And is there a line, even in an otherwise healthy patient, where you pull back?

DR STONE: Again, I mean, I’m glad this patient did well. I would not have treated him that way. I want to distinguish between fit for AML 3 + 7 therapy and likely to benefit. Monosomy 7, 83-year-old, not likely to benefit. I would have given him a hypomethylating agent. I mean, we don’t really know the right answer to these questions. My own view of this is that monosomy 7, 83-year-olds with mild dysplasia changes in the marrow have a very intrinsically resistant disease. He got into remission, but he’s likely to relapse.

So you have to really weigh the risks and benefits here. We don’t really have a prospective randomized trial of hypomethylating agent therapy, that is, azacitidine or decitabine versus 3 + 7.

What we do have is probably the best trial we have to look, to get some guidance, is a trial published by Hervé Dombret, largely conducted in Europe, AML-001, of azacitidine versus dealer’s choice. The doctor had to say before they went on the trial if they randomized to the control arm whether they would get 3 + 7, just supportive care or low-dose ara-C, which is used a lot in Europe.

And if you compare the results with the conventional care, which I just described, versus azacitidine, there was a longer median survival for those who were randomized to azacitidine. It wasn’t quite statistically significant. So I approach these people with both a fitness issue and the likely-to-benefit issue. And unless the patient has more favorable biology, I tend to use hypomethylating agents.

DR COLE: So to your point, when we decided to actually move forward with therapy, I did not have any of this information back about his monosomy 7 status. So I think sometimes you have to make a call, depending on your turnaround time.

DR STONE: How sick was he when he came in?

DR COLE: He was not terribly sick at that —

DR STONE: So I actually wait for that data to come back before I decide.

DR LOVE: How long does it take you to get that, Suzanne?

DR COLE: So it’s probably about a 14- to 16-day turnaround for us.

DR LOVE: Do you think he would have been clinically stable to wait?

DR COLE: Probably, but as somebody in the community, I don’t have that kind of experience to say, “I’m going to wait for 2 weeks on acute leukemia.” That’s kind of considered malpractice in my setting. You don’t wait. These people can bleed to death and die. And so that’s interesting that you can have that ability.

DR STONE: Even without the data and given his age, I would have given him azacitidine.

DR LOVE: Is there an age cutoff in, again, an otherwise healthy patient? Or you just stop —

DR STONE: I can’t remember treating with 3 + 7 someone older than age 80 in the recent past.

DR LOVE: Jorge, what are your thoughts about this issue of age and this case specifically?

DR CORTES: Yes. So a couple of things: (1), a cutoff. No, there’s no specific cutoff. When you talk about elderly AML, you see people putting the cutoff as low as 50 and 55, and, of course, that starts hurting now, because as you get closer to that or past that, anyway. And I think that there is a gray zone where we could make more of an argument for more intensive chemotherapy. But once you get past 70 to 75, I agree with what Rich mentioned that there are some individuals in that age group that are fit.

But there’s a couple of things: (1), Rich mentioned whether it’s going to help. And we pretty much know that it’s not going to help to those patients in any meaningful way. And (2), your fitness, physical fitness, still doesn’t account for the fact that your heart is also 85 and your kidneys are 85 and your liver is 85. So they’re going to end up more likely to have complications. So I do think that, at a certain point, the hypomethylating agents approach is a better deal.

Now, we also have to acknowledge that it’s not like we’re curing these patients, like, long term. But because these patients are not looking for 20-year survival for the most part, it’s an easier therapy, less likely to have them in the hospital, et cetera. And it does have some survival benefit. Even if some studies may not show it statistically significant, you’re not losing anything. If anything, you are gaining a little bit. So I do prefer to use these type of therapies.

I think that 1 important message is that, for the most part in these patients, you can wait for these tests, especially when they’re going to have some therapeutic implications or it is important to wait for them. Obviously you need to be watching them. And they’ll likely need transfusion support in the meantime, maybe some antibiotics, et cetera. But we have the same approach. We do wait for these results until we know what’s the best approach that we can offer to these patients.

DR LOVE: So before Lyle leaps out of his seat, because I can see the energy inside him, go for it.

DR FEINSTEIN: What if your late-seventies-/80-year-old patient had favorable-risk cytogenetics and had a good performance status? You talk about (1), whether or not the treatment is going to harm the patient and then whether or not the treatment is going to help the patient.

Now, if the patient has favorable-risk cytogenetics, my question is, is 7 + 3 induction followed by high-dose cytarabine consolidation the only way to cure someone with AML?

DR STONE: But if I do have a patient who’s fit and has favorable biology, I will use 3 + 7. And depending on the transplant center and the patient’s outlook, I will still transplant them with a reduced-intensity transplant if they’re fit enough.

DR FEINSTEIN: If they have favorable-risk cytogenetics?

DR STONE: I think that, if you look closely at the data, even favorable-risk older adults usually relapse. Now, we haven’t shown that taking a patient with an NPM1 mutation, normal karyotype who’s over 70, who’s 72, we should transplant them versus giving them consolidation chemo. You can be cured either way. So I think it’s a very controversial topic.

My own bias is that, if you can get a patient who’s older to minitransplant or reduced-intensity transplant, you do that. But if they couldn’t do it and want to, I think for the rare favorable older adult, I would treat them conventionally. I wouldn’t use high-dose ara-C. I would use modified high-dose ara-C but some fairly intensive consolidation.

DR CORTES: If I could just add to that, I do agree that a good-prognosis patient you probably would like to aim a little bit more. We have a slightly different approach, though. We don’t use 7 + 3 in any patient — and we can argue about those things. But in this kind of setting, older patient that I do want to intensify the ara-C, not just, like, low-dose ara-C, we use more like a FLAG kind of regimen. So we avoid the anthracycline. They seem to be more dependent on the higher doses of ara-C. And without the anthracycline, the myelosuppression is not as bad. The mucositis is not as bad.

There are some studies from the MRC that suggest that these patients, that FLAG actually may have some benefit over the standard chemotherapy in these patients. So the way we do it, we would do it on a patient like the one you mentioned, is more of a FLAG kind of regimen, fludarabine/cytarabine. They haven’t been compared, so it’s kind of different approaches. But that’s another way to try to do it, because there’s no question that these older patients, frequently their heart is already somewhat compromised in many instances.

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