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Getting Chronic Myelogenous Leukemia Into a Deeper Treatment Response

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Published on December 20, 2019

About 50 percent of chronic myelogenous leukemia patients who achieve a deep response can get off of therapy, says expert Dr. Jerry Radich, from Fred Hutchinson Cancer Research Center and Seattle Cancer Care Alliance. Can doctors predict who will respond well to treatment? On-site at the 2019 American Society of Hematology (ASH) Annual Meeting & Exposition, Dr. Radich describes the movement towards identifying which patients are likely to achieve a deeper response based on disease biology, how CML care is becoming more tailored to individuals and what conversations to have with your healthcare team about testing and treatment options. 

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Transcript | Getting Chronic Myelogenous Leukemia Into a Deeper Treatment Response

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Esther Schorr:

Hi there.  This is Esther Schorr with Patient Power, and I'm here at ASH 2019 in Orlando, and I'm very pleased to be here with Jerry Radich from the Fred Hutch in Seattle, and he is also affiliated with the Seattle Cancer Care Alliance, a wonderful organization there for cancer patients.  

So, doctor, please talk to us a little bit about what's going on here related to CML. 

Dr. Radich:

Sure.  As a background, now with patients with chronic phase disease put on any of the tyrosine kinases that are available life expectancy is almost normal.  Still, there are some patients who don't respond as well as they should.  And the other big issue is that there are people now who get a very, very deep response. And if they keep that for a period of time, they can actually get discontinued and be off therapy.  About 50 percent of them could get off therapy after a while. 

So the real movement right now is to identify patients who will be able to get that deep response, keep them there for a while, get them off therapy and predict who might be able to get off therapy and who won't, and then predict the people who are never going to get to that deep response and try to develop some strategy, therapeutic strategy to push them down a glide path so they can get into a deeper response and potentially be cured off therapy. 

Esther Schorr:

So predict what their response is going to be ahead of time. 

Dr. Radich:

Yes. 

Esther Schorr:

And then tailor the treatment…

Dr. Radich:

Exactly. 

Esther Schorr:

…to that. 

Dr. Radich:

Exactly. 

Esther Schorr:

Okay.  Interesting.  So how is that—how is that relevant for patients?  What can our patient audience take away from that in terms of the discussions they need to have with their oncologist? 

Dr. Radich:

Right.  So right now whether you get in a deep enough response at all is really one of the key issues.  And there are some patients who have been on drug for a while, they've been told by their doctor that they need to be on drug forever, and they would rather not have the uncertainty of getting off drug and then having to go back on if they relapse.  Even though it seems like that's a safe strategy.  There are some patients who basically say, I'm tolerating this drug fine.  I'll take it once a day for the rest of my life.  If that gives me normal life expectancy, wonderful, right? 

So one of the things is can we come up with ways that we make that bet a little bit more sure.  So before you—we offer you to discontinue therapy we can say based on this biology of your disease, you're going to be successful doing this versus, ay, it's not going to happen so why would we even go there, right?  So I think that's—we aren't ready to do that right now or tomorrow, but there's many avenues and investigators that are leaning that way, and I would suspect within a couple of years we'll have a pretty good way to predict whether people can safely get off therapy or not.  

Esther Schorr:

Okay.  So if that's if they do get off therapy.  Are there—is there an argument for staying on the therapy?  I mean, other than cost obviously, you know, if you have intermittent therapy it's less, but…

Dr. Radich:

The argument of staying on is that we know that people who have a successful response on therapy have essentially the same life expectancy as the normal population.  It's a pretty good argument, right? 

Esther Schorr:

Yeah. 

Dr. Radich:

So the other issue now is for people who are responding but maybe not as deeply and they would like to get off therapy because of financial reasons, because they're young and don't want to deal with the side effects for the rest of their life, because they're young and want to have children, are there therapeutic ways that we might be able to push them to a lower response.  So you're not responding quite well.  I can add an agent and get you down there. 

So the issue there is what agent.  So much of the work that's been going on here is to identify actually the biological pathways that are different between those people whose disease goes like this and those that go like that, because if you knew the biological difference between those you might have some new targets to turn a poor responder into a great responder. 

Esther Schorr:

So in CML then is it‑‑I know we've talked with other researchers here about MRD, or minimal residual disease, is that‑‑it sounds like in CML that's really important to get to that stage…

Dr. Radich:

Right. 

Esther Schorr:

…and then it…

Dr. Radich:

Right.  So minimal residual disease or now it's actually changing into measurable residual disease‑‑

Esther Schorr:

Yes. 

Dr. Radich:

…because we know there's actually nothing minimal about residual disease. 

Esther Schorr:

Either it's there or it's not. 

Dr. Radich:

And the implications, it's not good.  So CML was really the first place where we could actually monitor residual disease in the peripheral blood and actually get a very, very clear understanding of what disease burden was doing in a noninvasive way.  There's much effort that we and other people are doing outside of CML to get that kind of technology in the other leukemias so they wouldn't have to do multiple bone marrows.  And in other words sort of catching up to where CML is because CML is really the first one to demonstrate this. 

So, yes, we have at our disposal now a way to very conveniently, just with a blood draw, be able to know exactly what your disease burden is doing and how you're responding.  And so if you decide to do something else, to try another drug on top of a tyrosine kinase in a clinical trial, you wouldn't want to do that if it wasn't going to work because there's always going to be more side effects, but by following the peripheral blood BCR‑ABL you can very quickly decide whether or not it's working or not.  

Esther Schorr:

Right. 

Dr. Radich:

You don't have to wait a year or two years or so.  You can know within a month or so whether or not adding another agent is actually pushing you on the right glide path or not. 

Esther Schorr:

Okay.  So with all of that information, we have patients and their families who are listening to this.  What would you tell them to be discussing with their doctor with this new knowledge now? 

Dr. Radich:

Right.  So I think the main discussion is what is my BCR‑ABL level, the actual compliance to what we think are recommendation standards from the NCA and NELN aren't followed very well in the western world where we set the guidelines.  They aren't followed—and so the only way you're going to know what your disease burden is to measure it, right? 

So that was the first thing.  Where am I?  And what are the implications?  Is this something that is fine, I'm in a safe haven, I never have to worry about progression or resistance, versus is it low enough that I can think, me, maybe I can get off drug.  But that's truly something they shouldn't try on their own. 

Esther Schorr:

Right. 

Dr. Radich:

I mean, to get off drug outside of the context of a clinical trial you have to be willing to get testing like every month for four to six months to make sure that you're not one whose disease just comes rearing back, because it looks like this is safe.  If people's disease comes back, you introduce a tyrosine kinase it can push it down a lot, but you can't do that forever.  You can't let this thing go up and up and up and up and then six months from now discover that you have lots of disease and have risk of going into an accelerated phase of blast crisis. 

So if you want to do this at home outside of a clinical trial, you just have to have a pact with your doctor and yourself and your family that part of this is being monitored like a hawk for a while. 

Esther Schorr:

Okay.  So my last question then is, you've mentioned clinical trials.  Is there anything for CML patients that they should be aware of if they're looking to be in a clinical trial that's involved in all this? 

Dr. Radich:

Yeah.  There are a number of clinical trials run by either the institutions or by the U.S. inter groups, and they're really for a variety of indications.  There are discontinuation trials.  There are trials like I've described where you add another agent to get you to a lower level.  There are trials that you can get into at the very start of therapy.  So clinical trials are widely available throughout the country, and that's something that you should ask your private community doctor.  And if he doesn't know he can talk to his nearest academic center very and quickly find out.  

Esther Schorr:

Okay.  Great.  Dr. Jerry Radich, thank you very much for being here. 

Dr. Radich:

My pleasure.  

Esther Schorr:

We really appreciate it. 

Dr. Radich:

My pleasure. 

Esther Schorr:

A lot of good information.  

This is Esther Schorr from Patient Power.  And remember, knowledge can be the best medicine of all.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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