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Can CML Be Cured?

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Published on October 12, 2020

Clinical Trials Raise the Question: Can CML Be Cured?

Chronic Myeloid Leukemia (CML) is now considered a chronic disease, rather than a terminal disease, thanks to the recent FDA approval of five drugs for the treatment of CML: imatinib (Gleevec), dasatinib (Sprycel), nilotinib (Tasigna), bosutinib (Bosulif) and ponatinib (Iclusig). How have these drugs impacted the survivorship of CML? Is there a cure? Under what conditions are CML cancer patients able to stop treatment?

Dr. Eunice Wang, Chief of Leukemia Service at Roswell Park, joins Patient Power Co-Founder Andrew Schorr to share how current CML treatment is saving lives. This includes the combination therapies that are currently being studied, and how a clinical trial might be the key to decades of high quality living for CML patients moving forward.

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Transcript | Can CML Be Cured?

How have CML treatments changed in the past decade?

Andrew Schorr:
Hello, and welcome to Patient Power, I'm Andrew Schorr. Chronic myeloid leukemia has been tackled over the last decade or more now. And so many people are doing well, but there are different types of it, and everybody has their own different journey. Joining us now to help update us is Dr. Eunice Wang, Chief of the Leukemia Service at Roswell Park, Comprehensive Cancer Center in Buffalo, New York.

Dr. Wang, thank you for being with us.

Dr. Wang:
Thank you for the opportunity.

Andrew Schorr:
CML, if you go back more than 10 years, maybe 10, 12 years, it was not a great diagnosis, it affected often younger people as well. Where are we now?

What are the upsides and challenges of new Tyrosine Kinase Inhibitors?

Dr. Wang:
That's a great question. When I first started my training in the early 2000s, late 1990s, CML was a fatal disease. Patients got high dose chemotherapy, and all of them went for STEM cell transplant. We are now in the incredibly fortunate position where we have five pills that target a chronic phase CML.

The challenge now is to select the agents that are going to provide the best length of time. And taking consideration how effective these drugs are, that patients can realistically manage with their other co-morbidities and medical problems for the duration of their lifetime. There is emerging data that all of these pills when taken properly, and the majority of individuals can offer those individuals almost a normal life span.

The challenge now is how to use these drugs, to optimize and minimize the side effects. There're some studies that say, for the first 10 years, patients getting treated on some of these BCR-ABL inhibitors like imatinib (Gleevec) were no longer dying of their leukemia. But over 10 years, they were now dying from cardiac complications, which might've been exacerbated in part by the chemotherapy pills. So, this is the result of our success Andrew. We've now been able to cure the disease and now they're dying from other things. So that is the challenge for us.

Can you explain when and how patients may be able to stop therapy?

Andrew Schorr:
So there've been studies to say, well, could somebody CML be not back so well that they could stop therapy?

Dr. Wang:
So we have discovered that there's probably about 20 or 25% of patients that get treated with these BCR-ABL inhibitors, that their leukemia is extraordinarily sensitive to this inhibition.

And if you take these drugs for two or three years, you can get the disease into an undetectable state. So you can imagine you've been taking this pill now for three or four years, you can no longer detect by our most sensitive molecular assay, any evidence of the disease. So far, obviously, the question is, "Hey doctor, do I even need to take this anymore?" And in the past, we were terrified. Right? We were haunted by patients dying from CML in the 1990s.

And we said, "Don't stop." But it turns out until we stop, we won't know if the patient can be cured. And so in those 20 or 25% of individuals who have no detectable disease, we have been able to successfully stop the drug in about 50% of them. They can stop their drug. And the disease is so sensitive and so specific that the patient's own immune system can now take over the role of keeping that disease in check. And so now the focus and research in the field of CML is to see whether we can get more than 10 or 15% of people into that category.

Andrew Schorr:
What are some of the strategies to do that?

Dr. Wang:
So some of the strategies are, can we identify markers? Are there individual things that we can detect in you to say, "You will be successful, you will be one of the 50% that we can stop drug and we know that you're going to be successful?" Some of it is duration of time. So if you've been off drug and you've been undetectable for 10 years, you're much more likely to be able to stop drug than if you just got undetectable three years ago.

And the other strategy we've had is to look at adding other drugs. So many of the individuals are not eligible to stop drugs because their disease is not sensitive enough to the pill or to get them to that really low undetectable level. So, there's a lot of studies where we're trying to take other chemo pills or other agents adding them to the BCR-ABL inhibitors to enhance the ability of the BCR-ABL inhibitors, pushing that to an undetectable low level. And that hopefully when that's at that low level with the two drugs, not just the one drug at that point successfully stopping in those patients.

What is the course of action for CML patients who are newly diagnosed?

Andrew Schorr:
Dr. Wang, given that the pills that have been available for CML have been so successful if somebody is newly diagnosed now, should they still have a discussion with you or their doctor about being in a trial that might look at combination therapy to try to get a longer deeper remission or maybe being able to stop medicine forever at some point?

Dr. Wang:
I would recommend those individuals who are really seriously looking long-term and have a lot of comorbidities or complications and are anticipating having years, even decades of life to really seriously think about that. Because I think long-term, we don't know the side effects. And if we can get you cured, I think that that might offer the safest way to give you the best and longest life possible.

Andrew Schorr:
Dr. Wang there are some people who can stop taking their CML medicine, and there's a percentage that will never need it again. But if somebody might, is there a penalty for having gone off?

Dr. Wang:
No. As far as we know, with our current strategy, we recommend when patients stop the drug, that it's very important that they be carefully monitored. In our practice, we monitor patients when we stop the drug every month. And as soon as we see that their disease is growing back, and it's gotten back to a certain level, we restart the drug. And with that very careful monitoring, we have almost every individual, 99%, a hundred percent of individuals been able to get the disease back to an undetectable level.

So we do think it's important that patients that go off get carefully monitored. We've seen no adverse events if they're carefully monitored and they start to recur if we restart the drug. But I would caution individuals and I would advise them against just stopping taking the drug and not getting the careful monitoring. Because we have had individuals in that situation develop a more aggressive form of the disease. Who's shown up six or nine months later and had accelerated or a blast phase of the disease, which is almost like acute leukemia. So I think there are consequences of that, and it has to be done carefully under the management of your oncologist.

Andrew Schorr:
So Dr. Wang, when you put it all together for somebody newly diagnosed with CML now, it sounds like you have a great story for them really.

Dr. Wang:
Yes. I think we do. And I think it's a great success story that we have been able to develop such targeted and such effective therapies. I worked with medical fellows in my practice and I used to review their applications. And I have seen many, many applications where the individuals applying to be oncologists have been inspired by the success story of BCR-ABL inhibitors and targeted therapy in CML to go into oncology because it is so inspirational to them that over the last 20 years, they've taken a fatal disease and made it a chronic disease.

Andrew Schorr:
Wow. Well, it is a shining example and it's great news for patients diagnosed today or diagnosed years ago and living well. Dr. Eunice Wang from Roswell park, Comprehensive Cancer Center, thank you so much for being with us.

Dr. Wang:
Thank you.

Andrew Schorr:
I'm Andrew Schorr, remember knowledge can be the best medicine of all.


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