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Tweaking Treatments to Improve Survival

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Published on February 7, 2020

Chronic myelogenous leukemia expert Dr. Catriona Jamieson, from UC San Diego Moores Cancer Center, talks with Andrew Schorr about how doctors can tweak therapy to improve patient outcomes, and the importance of monitoring BCR-ABL levels for signs of resistance or progression. Dr. Jamieson also discusses the trajectory of genetic research for CML and explains how we've gotten to this point in terms of treatment and survival. Watch to hear a CML expert perspective.

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Transcript | Tweaking Treatments to Improve Survival

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.

Andrew Schorr:            

Hello, Andrew Schorr here in Orlando, Florida. This is where news is made at the ASH, American Society of Hematology annual meeting, and they discuss all sorts of blood conditions. Among them is CML, chronic myelogenous leukemia, and so they are myeloid specialists who talk about that a lot. Now, we’ve made tremendous progress with all sorts of TKIs that many of you may be taking. With me is a noted specialist, Dr. Catriona Jamieson from the Moores Cancer Center at UC San Diego. Thanks for being with us.

Dr. Jamieson:               

Thank you, Andrew.

Andrew Schorr:            

So, a few years ago, if you go back 10 years before imatinib (Gleevec), oh my God, terrible condition, and it was shortening peoples’ lives.

Dr. Jamieson:               

Right.

Andrew Schorr:            

Now, most people live a normal life. So, how are we tweaking what we’re doing in CML, so people can continue with a full life?

Dr. Jamieson:               

When you look at chronic myeloid leukemia, it’s an improbable story. We used to think we had to transplant that disease. It’s a leukemia, after all. You should be able to wipe it out with somebody else’s immune system, but at the cost of 25 percent mortality in the first year when we used to do full allogeneic transplants. So, then we started to say what else can we do and, more specifically, Brian Druker, Charles Sawyers, Owen Witte, Nick Lydon started to say let’s develop really effective therapies to target the gene we know is disabled or not working properly because of Janet Rowley, George Daley, David Baltimore, Rick van Etten… 

Andrew Schorr:            

…Philadelphia chromosome.

Dr. Jamieson:               

Philadelphia chromosome discovered in Philadelphia is 1960. At that time, we didn’t know what that meant. Janet Rowley created this fusion gene called BCR-ABL, and Brian Druker said, “Let’s target it.” I remember at the time people said, “No, that’s a disease that is diagnosed in 1 per 100,000 people in the U.S. That’s too small a market.” So companies didn’t want to develop it. Then, it just became this big ethical dilemma and debate. Because the company at the time who picked up this molecule and said okay, “Let’s try it.” It just moved forward with its own momentum and with patients pushing for it.

So now, not only do we have five TKIs, BCR-ABL inhibitors, we have very sensitive diagnostic tests so people can be followed, depending on where they are in their disease trajectory, every month or every three months to see where is their BCR-ABL level going in their blood. If it’s going into their boots, if they’re in complete molecular remission, some people are able to come off therapy. So, that’s the biggest advance in the field.

Andrew Schorr:            

Cessation.

Dr. Jamieson:               

Cessation. It’s called treatment-free remission, TFR, and that term was really coined for CML, because it’s the one disease where we said, “Okay, this is the one disease where it might be safe, because our techniques for detecting disease recurrence are so sensitive.”

Andrew Schorr:            

Molecular remission.

Dr. Jamieson:               

Molecular remission. We can get people back on TKIs before their body even notices.

Andrew Schorr:            

Is there a penalty? If somebody gets this cessation, do they pay a penalty for being off for a while?

Dr. Jamieson:               

Yes. I think when we first thought about treatment-free remissions, we were very excited. We thought of the people that get a complete molecular remission or very deep molecular response, then they should be able to come off. Well, it turns out two-thirds of people relapse within six months, and then the other third sometimes also go on to eventually progress. So, it means that the monitoring has to be extremely carefully done, and I think in the rush to get everybody off therapy, some people were left without any kind of follow-through or any follow-up, and that’s not the way we have to do…

Andrew Schorr:            

…to just say goodbye, see…

Dr. Jamieson:               

…yeah, they just said oh great, I don’t have to be on therapy. So, it’s sort of a mixed message. I think we have to be very careful with that. Now we’re saying at least seven years of zero detectable BCR-ABL transcripts, but in reality, when you look at the people that we’re able to maintain treatment-free remissions, meaning no therapy, no signs of disease, often they’d had interferon before.

So, I think you have to change the immune system’s ability to recognize these BCR-ABL positive cells as foreign to really sustainably get people off any kind of tyrosine kinase inhibition and that’s possible. You could give people an immune boost with natural killer cells or T cells that actually target a breakdown product of BCR-ABL or a protein that’s expressed.

Andrew Schorr:            

So, Dr. Jamieson, just to sum up where we are now, we have people living full lives with CML.

Dr. Jamieson:               

Absolutely, right.

Andrew Schorr:            

What a great success story. Thank you, Brian Druker and all the other people you mentioned. So, it sounds like there’s tweaking going on based on longer-term knowledge and sensitive tests. 

Dr. Jamieson:               

Absolutely. So, the tweaking is only necessary if people have side effects or they’re on-again-off-again in terms of taking their BCR-ABL inhibitors. So, you think about it, 90 percent of people who have managed to sustain BCR-ABL inhibition are alive and well not at 10 years, but up to 18 years later. So, we started the imatinib trials in around 2000 so it’s a long trajectory, actually up to 19 years. This is something that we’ve kind of come to expect. I think if we think about progression, why do people progress with CML, it’s usually because they came off therapy or they had an intolerance or resistance issues so we have to look for resistance mutations.

That’s the part we have to keep remembering to do, remember to check the BCR-ABL levels. It’s like staying on the same antihypertensive forever but not checking your blood pressure. You have to check your blood pressure to make sure it’s still working for you, because your kidney function can change, other things can change as we get older, so we have to be cognizant of that. Also, the tweaking really has to do with side effects. Sometimes people are fine on one BCR-ABL inhibitor and then they start to say, “You know, I’m a little short of breath. “ And so dasatinib, or Sprycel, is not going to be the best option for them.

Andrew Schorr:            

We have another.

Dr. Jamieson:               

But you have another one. So, we’ve got imatinib, dasatinib, nilotinib (Tasigna), ponatinib (Iclusig)_and bosutinib (Bosuliif). We have five inhibitors with different side effect profiles so that’s the tweaking. What’s the right tyrosine kinase inhibitor for you so you can stay on it? 

Andrew Schorr:            

At that time.

Dr. Jamieson:               

At this time so you can stay on this therapy long-term and have what we call an operational cure. So, an operational cure is a term that was coined by John Goldman in our field of CML where he said people are alive and well without signs or symptoms of disease and that’s fine.

Andrew Schorr:            

Amen.

Dr. Jamieson:               

Exactly.

Andrew Schorr:            

Well, it is one of the real success stories in blood cancers.

Dr. Jamieson:               

Absolutely.

Andrew Schorr:            

So, there’s still a responsibility for you, the patient, to make sure you’re being monitored appropriately and if you’ve stopped therapy, everybody needs to know what’s going on. You can’t just forget about it. Dr. Catriona Jamieson, thank you so much for being with us to talk about CML. 

Dr. Jamieson:               

Thanks so much. 

Andrew Schorr:            

Andrew Schorr, 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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