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Clinical Goals of Treating CML

Panelists:Jorge E. Cortes, MD, University of Texas MD Anderson Cancer Center; Harry P. Erba, MD, PhD, University of Alabama; Kevin Kelly, MD, PhD, University of Southern California; Javier Pinilla-Ibarz, MD, PhD, Moffitt Cancer Center; David S. Snyder, MD, FACP, City of Hope
Published: Sunday, Jan 24, 2016


Transcript:

Jorge Cortes, MD:
We have different treatment options now for frontline therapy. The field has evolved and we have, fortunately, many ways to treat our patients, so that brings the issue of how do you select between the different treatment options that we have available.

So, Javier, can you tell us a little bit of what factors you consider when you have a new patient and you’re trying to decide which of the drugs you’re going to use?

Javier Pinilla-Ibarz, MD, PhD: Absolutely, Jorge. As you very well know, every patient is different and I think to have a one-only approach for all patients is impossible. There is no doubt there are several factors that I consider, and many of us consider, when we discuss the multiple options for frontline therapy.

Age is an important factor in my opinion, as is the degree of the risk at disease at presentation, how active this person is at the time that he has come to our clinic, is this a parent, or working patient versus a patient who’s retired and has more time. Mainly these are the areas that I discuss; for sure, comorbidities and problems with health are an important factor to consider for the several TKIs that we have available, because some of them, or all of them, have different toxicity profiles that may or may not affect every patient whom we are going to treat with the drugs.

Jorge Cortes, MD: Yes, that’s very important. I guess in some way connected to this, is to look at what exactly is our goal for therapy in a particular patient. We know there are some differences between what we can achieve with these different drugs in terms of how quickly and how deep and all that.

May I ask you, Harry, what are your goals for therapy? What goals should we focus on when we’re starting to treat, that we need to keep an eye on that we reach? What do you look for when you’re treating a patient with CML?

Harry Erba, MD, PhD: Well, when I approach a patient with CML, as a hematologist and oncologist, my goals that I consider are the same as when I’m seeing a patient with any cancer. And the first question I consider is can I cure this disease and extend survival by doing so.

If I was only focused on cure, then I think all of our patients would still be undergoing allogeneic stem cell transplant at the time of diagnosis because we’re not quite certain yet if anyone will be cured with ABL tyrosine kinase inhibitors. But clearly we don’t do that because of the toxicity of that and the lack of donors for many patients.

And so the next thing I consider is how I can extend a person’s survival. Well, we’ve done much better, as you know, with ABL tyrosine kinase inhibitors in the last 10 to 15 years than therapy before it like with interferon. But I’ll remind everyone that no randomized trial has shown a survival benefit of an ABL TKI, over prior therapies, because these therapies become available and patients can switch.

Gleevec, imatinib have set the bar very high in terms of survival, so if it’s not survival then what is it? And for me the most important goal is the prevention of progression to accelerated phase and blast crisis. And it’s really important for the community oncologist to know that when we’re talking about progression, we’re not talking about losing a response and the white count goes up again and then you have time to find another ABL TKI.

Progression means that the biology of the disease has changed. The outcome of these patients is worse. Their survival is worse. They’re facing decisions about allogeneic transplant in that position, and when patients progress to accelerated phase or blast crisis, their median survival is about 10 months. And that’s been shown in the IRIS trial, in ENESTnd and other data sets. So prevention of progression becomes the most important goal in my book and treating patients with an agent that they can tolerate to do that is important.

The value of all of this discussion of cytogenetic responses and molecular responses, we need to remember really is the value of those endpoints, those response criteria in preventing progression down the road. So I would say for me is prevention of progression to accelerate phase and blast crisis. Getting rid of leukemic stem cell to finish with is not necessarily what I’m interested in, and we may not be able to do it with an ABL tyrosine kinase inhibitor.

To put it in a more practical term, I am not looking for all of my patients to become negative on a well done quantitative PCR, whether we call that an MR 4.5 or with these new digital PCRs that can detect even lower amounts of disease. We shouldn’t focus on that. We should focus on the responses that have correlated with and been associated with a lower rate of progression.

Jorge Cortes, MD: And I think that’s an important point. We need to remember that these response criteria are surrogate markers for these important endpoints.

Harry Erba, MD, PhD: Absolutely.

Jorge Cortes, MD: And we need to aim for good response but not being PCR negative is not necessarily a failure, very important points.
                                                                                                                                                                                                                                                                                                               
Transcript Edited for Clarity
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Transcript:

Jorge Cortes, MD:
We have different treatment options now for frontline therapy. The field has evolved and we have, fortunately, many ways to treat our patients, so that brings the issue of how do you select between the different treatment options that we have available.

So, Javier, can you tell us a little bit of what factors you consider when you have a new patient and you’re trying to decide which of the drugs you’re going to use?

Javier Pinilla-Ibarz, MD, PhD: Absolutely, Jorge. As you very well know, every patient is different and I think to have a one-only approach for all patients is impossible. There is no doubt there are several factors that I consider, and many of us consider, when we discuss the multiple options for frontline therapy.

Age is an important factor in my opinion, as is the degree of the risk at disease at presentation, how active this person is at the time that he has come to our clinic, is this a parent, or working patient versus a patient who’s retired and has more time. Mainly these are the areas that I discuss; for sure, comorbidities and problems with health are an important factor to consider for the several TKIs that we have available, because some of them, or all of them, have different toxicity profiles that may or may not affect every patient whom we are going to treat with the drugs.

Jorge Cortes, MD: Yes, that’s very important. I guess in some way connected to this, is to look at what exactly is our goal for therapy in a particular patient. We know there are some differences between what we can achieve with these different drugs in terms of how quickly and how deep and all that.

May I ask you, Harry, what are your goals for therapy? What goals should we focus on when we’re starting to treat, that we need to keep an eye on that we reach? What do you look for when you’re treating a patient with CML?

Harry Erba, MD, PhD: Well, when I approach a patient with CML, as a hematologist and oncologist, my goals that I consider are the same as when I’m seeing a patient with any cancer. And the first question I consider is can I cure this disease and extend survival by doing so.

If I was only focused on cure, then I think all of our patients would still be undergoing allogeneic stem cell transplant at the time of diagnosis because we’re not quite certain yet if anyone will be cured with ABL tyrosine kinase inhibitors. But clearly we don’t do that because of the toxicity of that and the lack of donors for many patients.

And so the next thing I consider is how I can extend a person’s survival. Well, we’ve done much better, as you know, with ABL tyrosine kinase inhibitors in the last 10 to 15 years than therapy before it like with interferon. But I’ll remind everyone that no randomized trial has shown a survival benefit of an ABL TKI, over prior therapies, because these therapies become available and patients can switch.

Gleevec, imatinib have set the bar very high in terms of survival, so if it’s not survival then what is it? And for me the most important goal is the prevention of progression to accelerated phase and blast crisis. And it’s really important for the community oncologist to know that when we’re talking about progression, we’re not talking about losing a response and the white count goes up again and then you have time to find another ABL TKI.

Progression means that the biology of the disease has changed. The outcome of these patients is worse. Their survival is worse. They’re facing decisions about allogeneic transplant in that position, and when patients progress to accelerated phase or blast crisis, their median survival is about 10 months. And that’s been shown in the IRIS trial, in ENESTnd and other data sets. So prevention of progression becomes the most important goal in my book and treating patients with an agent that they can tolerate to do that is important.

The value of all of this discussion of cytogenetic responses and molecular responses, we need to remember really is the value of those endpoints, those response criteria in preventing progression down the road. So I would say for me is prevention of progression to accelerate phase and blast crisis. Getting rid of leukemic stem cell to finish with is not necessarily what I’m interested in, and we may not be able to do it with an ABL tyrosine kinase inhibitor.

To put it in a more practical term, I am not looking for all of my patients to become negative on a well done quantitative PCR, whether we call that an MR 4.5 or with these new digital PCRs that can detect even lower amounts of disease. We shouldn’t focus on that. We should focus on the responses that have correlated with and been associated with a lower rate of progression.

Jorge Cortes, MD: And I think that’s an important point. We need to remember that these response criteria are surrogate markers for these important endpoints.

Harry Erba, MD, PhD: Absolutely.

Jorge Cortes, MD: And we need to aim for good response but not being PCR negative is not necessarily a failure, very important points.
                                                                                                                                                                                                                                                                                                               
Transcript Edited for Clarity
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