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Achieving Treatment-Free Remissions in CML

Panelists: Harry P. Erba, MD, Duke University; Jorge E. Cortes, MD, MD Anderson Cancer Center; Michael Mauro, MD, Memorial Sloan Kettering Cancer Center
Published: Wednesday, Aug 29, 2018



Transcript: 

Harry P. Erba, MD: Thanks. OK, so let’s move on to our last major topic and what’s really new to consider in our patients, and that’s treatment-free remissions in CML. I want to just start by saying this is not just giving patients a drug holiday, this isn’t just saying, “Oh, you’re going on vacation, you don’t want to have this or that side effect, why don’t you hold the drug for a little bit and then restart?” Treatment-free remissions, as we’re going to talk about, are really a very active part of a patient’s therapeutic course with CML. And so, we’re going to talk specifically about that. Jorge, let’s start with how do we identify patients who may be eligible for treatment-free remissions and which patients in your practice have actually asked you about and truly considered treatment-free remissions?

Jorge E. Cortes, MD: I think that the guidelines that we use today for considering treatment-free remissions are kind of like doing it in general practice. They also are the ones that were established in the original studies that came from France, the STIM and TWISTER studies, respectively. So, those were patients who had achieved and maintained a deep molecular response. In those studies, those laboratories have very deep PCR and they went undetectable with a 5-log level of detection. We’ve extrapolated that to MR4.5. So, a sustained MR4.5 for at least 2 years was the minimum that they required for those studies, with at least 5 assessments during those 2 years. That means you’ve been doing it every 6 months, as has been recommended as we mentioned earlier. Those studies were done with imatinib, by the way. In those patients, they considered a treatment discontinuation. As important as it is to consider who is eligible, another important thing to consider is what do you do after that. They were monitored very, very closely, every month. Actually, in some of these studies, they did every month for the first year, and then every 2 months, and then every 3 months. And the other thing that’s important in those studies is that those studies resumed therapy as soon as a PCR became detectable.

But in terms of answering your question, I think we can address the other issues later. But I think that today we need to consider it for patients who have at least 2 years of a sustained MR4.5. I address it to my patients. Everybody who meets those criteria, I bring it up. Some patients bring it up themselves because they discuss it and they hear it, and all of that. So, of course, some of them bring it up when they do not meet those criteria, so you need to educate them. But it’s a good thing because then you can focus and say, “Let’s aim for that and explain what things can help them, from adherence to optimizing doses, and all these kinds of things.”

Curiously, my batting average is pretty low in terms of treatment discontinuation. I’ve had few takers, relatively speaking. I have stopped therapy. Now I have a series of almost 200 patients where I’ve stopped therapy, but that still represents a very small percentage of my practice. But part of that is because we all did these when we started treating those patients who now are eligible, we were telling them don’t ever miss a dose, and we told them that the treatment was forever. We didn’t know about these things, now we do. So, what I do now is when I start a patient on treatment, I tell them the treatment is forever. However, we are starting to understand that some patients may lead to treatment discontinuation, and this is what we need to…if you get to this point, let them know that it may be a possibility for them and it actually probably helps them have the motivation for adherence, for aiming, the monitoring and all these things because it looks like I may get to that. It’s possible.

Harry P. Erba, MD: I agree. I think it does make it part of the initial discussion with patients. The other thing you brought up was just how long you need to be in an MR4.5. And I’m going to have Mike talk about a summary of all of these many, many studies now that have looked at thousands of patients where we’ve had treatment discontinuations. In an effort to harmonize all of these studies into one recommendation, the NCCN recently said that patients need to be on an ABL TKI for at least 3 years and that last year be in a stable MR4.5. But it’s to try to bring some uniformity to a recommendation based on studies that have all varied in how they’ve done it.

Transcript Edited for Clarity 

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Transcript: 

Harry P. Erba, MD: Thanks. OK, so let’s move on to our last major topic and what’s really new to consider in our patients, and that’s treatment-free remissions in CML. I want to just start by saying this is not just giving patients a drug holiday, this isn’t just saying, “Oh, you’re going on vacation, you don’t want to have this or that side effect, why don’t you hold the drug for a little bit and then restart?” Treatment-free remissions, as we’re going to talk about, are really a very active part of a patient’s therapeutic course with CML. And so, we’re going to talk specifically about that. Jorge, let’s start with how do we identify patients who may be eligible for treatment-free remissions and which patients in your practice have actually asked you about and truly considered treatment-free remissions?

Jorge E. Cortes, MD: I think that the guidelines that we use today for considering treatment-free remissions are kind of like doing it in general practice. They also are the ones that were established in the original studies that came from France, the STIM and TWISTER studies, respectively. So, those were patients who had achieved and maintained a deep molecular response. In those studies, those laboratories have very deep PCR and they went undetectable with a 5-log level of detection. We’ve extrapolated that to MR4.5. So, a sustained MR4.5 for at least 2 years was the minimum that they required for those studies, with at least 5 assessments during those 2 years. That means you’ve been doing it every 6 months, as has been recommended as we mentioned earlier. Those studies were done with imatinib, by the way. In those patients, they considered a treatment discontinuation. As important as it is to consider who is eligible, another important thing to consider is what do you do after that. They were monitored very, very closely, every month. Actually, in some of these studies, they did every month for the first year, and then every 2 months, and then every 3 months. And the other thing that’s important in those studies is that those studies resumed therapy as soon as a PCR became detectable.

But in terms of answering your question, I think we can address the other issues later. But I think that today we need to consider it for patients who have at least 2 years of a sustained MR4.5. I address it to my patients. Everybody who meets those criteria, I bring it up. Some patients bring it up themselves because they discuss it and they hear it, and all of that. So, of course, some of them bring it up when they do not meet those criteria, so you need to educate them. But it’s a good thing because then you can focus and say, “Let’s aim for that and explain what things can help them, from adherence to optimizing doses, and all these kinds of things.”

Curiously, my batting average is pretty low in terms of treatment discontinuation. I’ve had few takers, relatively speaking. I have stopped therapy. Now I have a series of almost 200 patients where I’ve stopped therapy, but that still represents a very small percentage of my practice. But part of that is because we all did these when we started treating those patients who now are eligible, we were telling them don’t ever miss a dose, and we told them that the treatment was forever. We didn’t know about these things, now we do. So, what I do now is when I start a patient on treatment, I tell them the treatment is forever. However, we are starting to understand that some patients may lead to treatment discontinuation, and this is what we need to…if you get to this point, let them know that it may be a possibility for them and it actually probably helps them have the motivation for adherence, for aiming, the monitoring and all these things because it looks like I may get to that. It’s possible.

Harry P. Erba, MD: I agree. I think it does make it part of the initial discussion with patients. The other thing you brought up was just how long you need to be in an MR4.5. And I’m going to have Mike talk about a summary of all of these many, many studies now that have looked at thousands of patients where we’ve had treatment discontinuations. In an effort to harmonize all of these studies into one recommendation, the NCCN recently said that patients need to be on an ABL TKI for at least 3 years and that last year be in a stable MR4.5. But it’s to try to bring some uniformity to a recommendation based on studies that have all varied in how they’ve done it.

Transcript Edited for Clarity 
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