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The Risk-Stratifying Factors in CLL

Panelists: William G. Wierda, MD, PhD, The University of Texas MD Anderson Cancer Center; Steven Coutre, MD, Stanford University Medical Center; Matthew S. Davids, MD, MMSc, Dana-Farber Cancer Institute; Nicole Lamanna, MD, Columbia University Medical Center; Shuo Ma, MD, PhD, Robert H. Lurie Comprehensive Cancer Center
Published: Friday, Jan 12, 2018



Transcript: 

William G. Wierda, MD, PhD: Thank you for joining this OncLive® Peer Exchange® entitled “Refining Therapy for Chronic Lymphocytic Leukemia.” The availability of novel therapies for CLL has drastically improved outcomes but has also increased the complexity of treating symptomatic patients. Moreover, there remains a substantial unmet need for many patients who relapsed. In this Peer Exchange® panel discussion, my colleagues and I will shed light on how best to use these available therapies. We’ll review the latest data, including studies from ASH 2017, looking at novel agents, novel combinations, and the impact on sequencing therapies for patients with relapsed or refractory CLL.

I’m Dr. William Wierda, D.B. Lane Cancer Research Distinguished Professor of Medicine, head of the CLL Section and medical director for the Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston, Texas. Joining me for this discussion are Dr. Steven Coutre, professor of medicine for hematology at Stanford University School of Medicine in Stanford, California; Dr. Matthew Davids, assistant professor of medicine at Harvard Medical School and associate director of the CLL Center at the Dana-Farber Cancer Institute in Boston, Massachusetts; Dr. Nicole Lamanna, associate professor of medicine, director of CLL at Columbia University, New York; and Dr. Shuo Ma, associate professor of medicine in the Division of Hematology/Oncology at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Thank you for joining us, let’s begin.

So, there have been dramatic changes in management for patients with CLL, but I’d like to first talk about when patients are initially diagnosed and what workup we do for those patients. Routinely, patients are identified as having an elevated absolute lymphocyte count by their primary care provider, typically, and they’re referred to a hematologist for the standard workup and evaluation. So, maybe we can start with Nicole and maybe you can comment on the workup, what prognostic factors do we need for the initial evaluation of patients, and how those are useful.

Nicole Lamanna, MD: Absolutely. I think it’s really important, first of all, that the initial workup for the patient is mostly spending a great deal of time talking about their disease. If they don’t have cytopenias, routine blood work should include peripheral blood studies, including cytogenetic FISH analysis looking for prognostic markers—the unmutated IGVH, of course—and peripheral blood flow cytometry. CAT scanning always becomes an issue, I think, depending upon where you practice. I typically do not routinely image my patients. A good physical exam is fine unless the patient has a focal complaint or there’s something that I am concerned about. If they have very bulky lymphadenopathy on their peripheral exam that I’m concerned about how big is the bulky lymphadenopathy in the abdominal region, then perhaps I will scan them just to see. But it is not routine practice that I image patients. So, typically, peripheral blood studies are done first, then spending a great deal of time talking with the patients about their CLL and their biology once you get all those routine studies back.

I do typically in the first visit also include their hepatitis serologies. I’ll also look at their quantitative immunoglobulin levels and some other things, routine organ function, liver studies, kidney function, so on and so forth. But I think it’s most important to ascertain their prognostic markers at their first visit.

William G. Wierda, MD, PhD: So, it is important to get that information upfront.

Nicole Lamanna, MD: Yes.

William G. Wierda, MD, PhD: Do we absolutely need it? What’s it useful for?

Nicole Lamanna, MD: Obviously, I think an argument can be made. And as we get into an era of more cost containment and issues regarding cost, if somebody does not need treatment, there could be an argument to be made that you’re doing those studies before somebody does need treatment because it can influence the type of therapies that you will then use subsequent to that. So, if somebody does not obtain their FISH analysis or their IGVH status at the initial visit, you probably can’t fault them for that. Of course, when you want to talk to them about potentially their time to initiate therapy, not having that data, there is some relevance of not knowing that information. But truthfully, you really need it prior to starting therapy when you’re talking about treatments.

William G. Wierda, MD, PhD: And maybe we can have a little discussion about the patient population that’s most commonly affected with CLL and considerations with regard to that population, not only in the time that patients need to be treated, but prior to their treatments. So maybe, Steve, you can comment on who are mostly affected by CLL. What are the issues with that population?

Steven Coutre, MD: I think sometimes we lose sight of the fact that the average patient is 72 to 75 years old at diagnosis, and the average patient doesn’t need treatment. So, the average patient comes to treatment in their 70s and we can talk about that when we talk about choosing initial treatment. But it’s a really important point because these are older patients, mostly, and so there’s often a lot of comorbidities and we have to take that into consideration.

Now from the prognostic factor standpoint, I often get patients not so much straight from the internist to make a diagnosis. I get them from a colleague in the community. And the patient who has been told, “You have leukemia, and you’re not going to get treatment.” And so, of course, many are like, “Well, what does that mean?” And so, as Nicole said, spend a great deal of time talking about that.

I have a discussion of the prognostic factors, and an individual patient can decide whether they want to pursue those. They’re just blood tests, but they’re expensive. And remember, patients like to refer to themselves as, we call it watch-and-wait, watch-and-worry. And so, I always say, “Well, if we get this information, you’re either going to be happy because you have a favorable profile or you’re going to worry even more because you have a less favorable profile.” But I’m not going to do anything about treatment based on the information I get. So, I think it’s really important to really inform the patient about expectations.

William G. Wierda, MD, PhD: Great. Matt, maybe you can comment on which factors might be useful in predicting time to first treatment.

Matthew S. Davids, MD, MMSc: I think first and foremost, we look at the FISH tests because it gives us a very good sense. We know that about half of the patients will have a deletion 13q, which is very favorable. But a smaller subset of the diagnosis, in the range of 8% to 10%, are going to have the deletion 17p. We know those patients on average may need treatment within the first couple of years after diagnosis. And I do find that helpful in counseling patients. It also informs the frequency of observation visits. If I have a new patient with deletion 17p, I might see them every 2 or 3 months initially. Whereas if I have another patient on observation with 13q, that might be every 6 months.

So, I think there are some practical implications. I think the IGVH mutation status is also a helpful piece of information to know. That tends to be a stable prognostic marker, meaning that it doesn’t change over time. So, if you’re ever going to check it, to me it makes sense to check it at diagnosis and then you have that piece of information. But I certainly agree with the sentiment that patients need to decide how much information they want to know, so it really is an individualized discussion with each patient. There are some other factors to consider. Beta-2 microglobulin can be a helpful test to obtain as well.

I have a similar approach to Nicole, I think, in terms of imaging. The one situation I do sometimes routinely image is in patients who have deletion 17p, or deletion 11q in particular. Even if they’re asymptomatic, sometimes they can have bulky internal lymphadenopathy and I want to know that at baseline. But outside of that, routine imaging and routine bone marrow biopsies are not necessarily a diagnosis.

William G. Wierda, MD, PhD: I think that’s an important point. So, in terms of initial workup, patients don’t need a bone marrow. The prognostic factors can be done just as easily and as reliably on blood so we can get all the information we need initially.

Transcript Edited for Clarity 

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Transcript: 

William G. Wierda, MD, PhD: Thank you for joining this OncLive® Peer Exchange® entitled “Refining Therapy for Chronic Lymphocytic Leukemia.” The availability of novel therapies for CLL has drastically improved outcomes but has also increased the complexity of treating symptomatic patients. Moreover, there remains a substantial unmet need for many patients who relapsed. In this Peer Exchange® panel discussion, my colleagues and I will shed light on how best to use these available therapies. We’ll review the latest data, including studies from ASH 2017, looking at novel agents, novel combinations, and the impact on sequencing therapies for patients with relapsed or refractory CLL.

I’m Dr. William Wierda, D.B. Lane Cancer Research Distinguished Professor of Medicine, head of the CLL Section and medical director for the Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston, Texas. Joining me for this discussion are Dr. Steven Coutre, professor of medicine for hematology at Stanford University School of Medicine in Stanford, California; Dr. Matthew Davids, assistant professor of medicine at Harvard Medical School and associate director of the CLL Center at the Dana-Farber Cancer Institute in Boston, Massachusetts; Dr. Nicole Lamanna, associate professor of medicine, director of CLL at Columbia University, New York; and Dr. Shuo Ma, associate professor of medicine in the Division of Hematology/Oncology at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Thank you for joining us, let’s begin.

So, there have been dramatic changes in management for patients with CLL, but I’d like to first talk about when patients are initially diagnosed and what workup we do for those patients. Routinely, patients are identified as having an elevated absolute lymphocyte count by their primary care provider, typically, and they’re referred to a hematologist for the standard workup and evaluation. So, maybe we can start with Nicole and maybe you can comment on the workup, what prognostic factors do we need for the initial evaluation of patients, and how those are useful.

Nicole Lamanna, MD: Absolutely. I think it’s really important, first of all, that the initial workup for the patient is mostly spending a great deal of time talking about their disease. If they don’t have cytopenias, routine blood work should include peripheral blood studies, including cytogenetic FISH analysis looking for prognostic markers—the unmutated IGVH, of course—and peripheral blood flow cytometry. CAT scanning always becomes an issue, I think, depending upon where you practice. I typically do not routinely image my patients. A good physical exam is fine unless the patient has a focal complaint or there’s something that I am concerned about. If they have very bulky lymphadenopathy on their peripheral exam that I’m concerned about how big is the bulky lymphadenopathy in the abdominal region, then perhaps I will scan them just to see. But it is not routine practice that I image patients. So, typically, peripheral blood studies are done first, then spending a great deal of time talking with the patients about their CLL and their biology once you get all those routine studies back.

I do typically in the first visit also include their hepatitis serologies. I’ll also look at their quantitative immunoglobulin levels and some other things, routine organ function, liver studies, kidney function, so on and so forth. But I think it’s most important to ascertain their prognostic markers at their first visit.

William G. Wierda, MD, PhD: So, it is important to get that information upfront.

Nicole Lamanna, MD: Yes.

William G. Wierda, MD, PhD: Do we absolutely need it? What’s it useful for?

Nicole Lamanna, MD: Obviously, I think an argument can be made. And as we get into an era of more cost containment and issues regarding cost, if somebody does not need treatment, there could be an argument to be made that you’re doing those studies before somebody does need treatment because it can influence the type of therapies that you will then use subsequent to that. So, if somebody does not obtain their FISH analysis or their IGVH status at the initial visit, you probably can’t fault them for that. Of course, when you want to talk to them about potentially their time to initiate therapy, not having that data, there is some relevance of not knowing that information. But truthfully, you really need it prior to starting therapy when you’re talking about treatments.

William G. Wierda, MD, PhD: And maybe we can have a little discussion about the patient population that’s most commonly affected with CLL and considerations with regard to that population, not only in the time that patients need to be treated, but prior to their treatments. So maybe, Steve, you can comment on who are mostly affected by CLL. What are the issues with that population?

Steven Coutre, MD: I think sometimes we lose sight of the fact that the average patient is 72 to 75 years old at diagnosis, and the average patient doesn’t need treatment. So, the average patient comes to treatment in their 70s and we can talk about that when we talk about choosing initial treatment. But it’s a really important point because these are older patients, mostly, and so there’s often a lot of comorbidities and we have to take that into consideration.

Now from the prognostic factor standpoint, I often get patients not so much straight from the internist to make a diagnosis. I get them from a colleague in the community. And the patient who has been told, “You have leukemia, and you’re not going to get treatment.” And so, of course, many are like, “Well, what does that mean?” And so, as Nicole said, spend a great deal of time talking about that.

I have a discussion of the prognostic factors, and an individual patient can decide whether they want to pursue those. They’re just blood tests, but they’re expensive. And remember, patients like to refer to themselves as, we call it watch-and-wait, watch-and-worry. And so, I always say, “Well, if we get this information, you’re either going to be happy because you have a favorable profile or you’re going to worry even more because you have a less favorable profile.” But I’m not going to do anything about treatment based on the information I get. So, I think it’s really important to really inform the patient about expectations.

William G. Wierda, MD, PhD: Great. Matt, maybe you can comment on which factors might be useful in predicting time to first treatment.

Matthew S. Davids, MD, MMSc: I think first and foremost, we look at the FISH tests because it gives us a very good sense. We know that about half of the patients will have a deletion 13q, which is very favorable. But a smaller subset of the diagnosis, in the range of 8% to 10%, are going to have the deletion 17p. We know those patients on average may need treatment within the first couple of years after diagnosis. And I do find that helpful in counseling patients. It also informs the frequency of observation visits. If I have a new patient with deletion 17p, I might see them every 2 or 3 months initially. Whereas if I have another patient on observation with 13q, that might be every 6 months.

So, I think there are some practical implications. I think the IGVH mutation status is also a helpful piece of information to know. That tends to be a stable prognostic marker, meaning that it doesn’t change over time. So, if you’re ever going to check it, to me it makes sense to check it at diagnosis and then you have that piece of information. But I certainly agree with the sentiment that patients need to decide how much information they want to know, so it really is an individualized discussion with each patient. There are some other factors to consider. Beta-2 microglobulin can be a helpful test to obtain as well.

I have a similar approach to Nicole, I think, in terms of imaging. The one situation I do sometimes routinely image is in patients who have deletion 17p, or deletion 11q in particular. Even if they’re asymptomatic, sometimes they can have bulky internal lymphadenopathy and I want to know that at baseline. But outside of that, routine imaging and routine bone marrow biopsies are not necessarily a diagnosis.

William G. Wierda, MD, PhD: I think that’s an important point. So, in terms of initial workup, patients don’t need a bone marrow. The prognostic factors can be done just as easily and as reliably on blood so we can get all the information we need initially.

Transcript Edited for Clarity 
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