DR FEINSTEIN: So I’m actually particularly interested in the whole idea about referring older patients with, quote, favorable cytogenetics for transplant based on the fact that they are older. And I think mainly it’s because recently I’ve had 2 patients who were 70-plus years of age or older and who I’ve given induction chemotherapy to. And we’ve waited for their cytogenetic profile to come back, and it was favorable. And I’ve had that conversation with them that, “No, we do not have to send you right now for transplant evaluation.” Is there an arbitrary age cutoff that you would send all physically fit 70-plus-year-old patients for transplant evaluation?

DR STONE: That’s a great question. Seriously. It’s a data-free zone, in my opinion. What do you do with a favorable-risk older adult who, if they were younger, we would not transplant? That’s basically what we’re talking about.

I, in my own mind — and it’s not based on any data — have looked at the data. And I’ve noted that the outcome even in the favorable older adult, while it’s more favorable than our older adult colleagues, it’s still not very good. And, in most cases, transplant will only increase that. So even if you get a 30% or 35% cure rate, because they don’t have NPM1 mutation or FLT3 wild type and they’ve gone into remission, it’s still not very good. And I think transplant would probably be superior, but it takes a real close — I mean, if they had a 30% cure rate and they were younger, you would certainly send them for transplant, right? So why would you do that for a fit older adult? That’s my reasoning for sending them to transplant.

Now, they have to know that there’s a big up-front risk, 10% to 15% mortality. It really depends on what their goals are. If they want to be alive when they’re 75, I’d say, “Go to transplant.” If they want to be alive when they’re 70, if they’re 68, let’s say, then don’t have a transplant. Just take chemotherapy and hope for the best, and only get transplanted if you relapse and go into second remission, which is an iffy proposition. So my own view is, if you’re above age 60 and you have favorable chromosomes, I at least have a discussion about stem cell transplant with the patient.

DR CORTES: I like the expression that Rich used, that this is a data-free zone, and that is true. If you would ask 30 investigators about what they would do, you’d get 45 answers. And that’s because we really don’t know what’s the best approach. I would approach it different. I would not send these patients straight to transplant based on age. I think he has a good prognosis. And my guess, just knowing my transplant colleagues in my institution, is that, if I would send them to transplant, which we routinely do, these patients, just so that they have the conversation and start looking for donors in case we need them now or later, et cetera, my guess is that they will send them back to me and say, “Fine. Thank you, but not right now.”

And also, our guys are pretty aggressive. That’s the other thing, that depending on where you send them to transplant, transplant groups, some of them are a little bit more aggressive in terms of what patients they take, age-wise and performance status-wise and risk-wise, et cetera. And some are a little bit more conservative. So let’s not forget that not many years ago, at age 55 you would stop, period. There was no discussion. That was it in transplanting patients. So I think there’s a lot of our ability — and all of that comes to the fact that it’s because we don’t have data. We have experience and opinions and things like that, but that’s it.

DR STONE: I was really thinking about word usage. What is targeted therapy? It’s become so overused it has lost its meaning. So I tried to talk about what targeted therapy really means. I mean, daunorubicin is targeted therapy, right? I mean, it targets topoisomerase 2. So nobody would go around saying, “Daunorubicin is targeted therapy.”

So there’s some principles that were imparted to me by the father, in my opinion, of modern targeted therapy, my colleague Brian Druker, who developed imatinib for CML, along with drug companies and other doctors. But the target should be present only on the malignant cell. It should be not present on cells you don’t want to kill. It should be definitely required for leukemic survival, critically, and getting rid of it should not be a problem for normal physiology.

So, I mean, it’s easier to think about IDH mutations and FLT3 mutations as targeted therapy. Is a Bcl-2 inhibitor targeted therapy? I think it’s targeted, but not in the same way. So I think that’s just something to think about when we consider what is targeted therapy and what is not and what is a true silver bullet and what is not. It’s very hard to come up with a true silver bullet, because normal physiology is only slightly deranged when we’re talking about cancer.

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