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Timing of Second-Line Therapy in Follicular Lymphoma

Panelists: Ian W. Flinn, MD, PhD, Sarah Cannon Research Institute; Joshua Brody, MD, Icahn School of Medicine at Mount Sanai; Nathan H. Fowler, MD, University of Texas MD Anderson Cancer Center; John P. Leonard, MD, New York Presbyterian/Weill Cornell Medical Center; Matthew Lunning, DO, University of Nebraska Medical Center; Sonali M. Smith, MD, University of Chicago
Published: Friday, Aug 03, 2018



Transcript: 

Ian W. Flinn, MD, PhD: Let’s turn to relapsed follicular lymphoma and the decision regarding when to treat the next patient after they’ve already had a therapy. We have these criteria that have been written down for frontline with normal indications for treatment—bulky disease, cytopenias, pleural infusions, things like that; symptoms. Nate, are you using those same criteria in patients with their second treatment?

Nathan H. Fowler, MD: Yes, with the exception that if I go back to the frontline, I do tend to use GELF. I’m pretty religious about using GELF criteria to determine when patients require treatment. In fact, when I first see patients in clinic, I tell them about the GELF criteria, so they’re actually following along with me when we’re looking at scans together and following their blood counts; they understand when we’re getting close to needing treatment.

Then, once they have treatment, I often think about other factors when I’m initiating a second or third line; that may become how long their first remission lasted; how it presents, either as a large bulky disease or a low-volume disease; and how the patient feels about the relapse. For example, if I have a patient who receives induction chemotherapy with Rituxan (rituximab) and they go 8 years, I’m probably not going to do chemotherapy again. I’ll just give them more Rituxan because they’ve shown to me that they’re a very low-risk patient. I might use that Rituxan earlier, even before they have progression of disease or symptoms—again, because I get the sense that I can control them with not a lot of therapy. I do think that I use the GELF as a hard fast, so if they have symptoms, I’m not going to watch and wait with patients in the relapsed setting. But I guess what I’m saying is I may treat patients a little earlier, before they actually develop GELF criteria in the relapsed setting, depending on how long their remission is.

Joshua Brody, MD: It’s rare that they’ll have better kinetics on their recurrence than they had in their initial presentation. If they quickly progressed needing more therapy the first time around, you can see that it’s going to happen again.

Nathan H. Fowler, MD: As we’ve seen from data, the patients that go at least 2 years, they’re probably never going to die of their disease. That’s really nice, because what that tells me is, most of the patients had very heterogenous therapy in the second and third line, but despite that, their survivals all were very, very good long term.

Matthew Lunning, DO: So, do you stop doing surveillance imaging, is the question. I think about it as, if we’re not doing surveillance imaging, are you capturing their relapse on physical exam or some laboratory finding, or a complaint that prompts a scan, versus doing active surveillance in a symptomatic individual and capturing borderline GELF criteria? You don’t then know the velocity of that change. I think that that’s an important piece. If you’re not doing scans, you may acknowledge that you have nodes that are growing, but you feel well. Maybe we look again, and to your point, if it’s after 2 years after their first line of therapy, then that might be a slow relapser, and it may have been relapsing for a very long time.

John P. Leonard, MD: I would suspect, that with someone who has a known history of follicular lymphoma, that the burden of disease they present with at relapse—and I clinically detect the relapse—is probably lower than when they were diagnosed in general. Because you’re seeing them, you’re examining their nodes, they’re more attentive, et cetera. Even in the absence of scans, I think that the first relapse tends to be diagnosed earlier. The exception may be transformation—when the patient will come in with a bulky mass or rapid progression. But I think either way, if your approach is to use more minimal treatment or to take your time with a first relapsed patient, you’re probably going to find those at a state where the patient has less disease going on.

Sonali M. Smith, MD: The challenge that I’m having is that, first of all, this whole early progression of disease is something that we are just now aware of. Sometimes you’ll have somebody who progresses early, but they don’t actually need treatment. So, you know their prognosis is not going to be great, but it’s not really clear that you need to intervene at that time. I think that’ll be the next generation of questions.

Ian W. Flinn, MD, PhD: It’s probably an important one. The other thing that you bring up here in this discussion about scans; we live in this era where everyone says to do less scans. Of course, they’re not without harm, scans. At the same time, you can’t really tell if someone progresses unless they get very symptomatic. Have you changed how often you do scans or if you do scans?

Sonali M. Smith, MD: I try very hard not to do scans unless somebody has symptoms, change in blood work, or a change in exam. I think, again, I’ve just started to really take the long view. You look at some of these long-term data sets and know that they’re going to be alive 10, 15, maybe 20 years later. So, I try very hard. Unless they’re part of some particularly high-risk background, I try not to do the scans.

Ian W. Flinn, MD, PhD: Nathan, does that matter how far out you are from therapy? The first 2 years versus 5 years?

Nathan H. Fowler, MD: Yes, so I may be an outlier in the group. I am still a believer in imaging. I think that regarding what you mentioned earlier, I tend to do more intense imaging in the first year because, again, I’m thinking about transformation. Am I missing an occult transformation? Generally, I’ll do a scan about 3 months after they finish their first therapy and then 3 to 6 months again. Very quickly I start moving to annual imaging if I’m kind of ruling out any aggressive course. As you mentioned, if they have a fairly long remission—in other words, you’re talking 2 or 3 years—we start really reducing imaging, and often in patients who are several years out, all they’re getting, for example, is a chest x-ray, blood work, and physical exam.

Ian W. Flinn, MD, PhD: This is all CT scans. Do you do a PET scan after therapy at all?

Nathan H. Fowler, MD: In the United States…and I’ll just say that imaging often is dictated by insurance companies, so I think PET imaging is actually a much better modality for following a follicular lymphoma patient. When I’m talking about PET, I’m talking about a PET-CT. Current PET-CTs have essentially the same amount of radiation as a standard CT. So, again, I think that if I was to follow a patient and I could do whatever I wanted, I would probably use PET-CTs in patients; but CT scans are currently what’s approved.

Transcript Edited for Clarity 

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Transcript: 

Ian W. Flinn, MD, PhD: Let’s turn to relapsed follicular lymphoma and the decision regarding when to treat the next patient after they’ve already had a therapy. We have these criteria that have been written down for frontline with normal indications for treatment—bulky disease, cytopenias, pleural infusions, things like that; symptoms. Nate, are you using those same criteria in patients with their second treatment?

Nathan H. Fowler, MD: Yes, with the exception that if I go back to the frontline, I do tend to use GELF. I’m pretty religious about using GELF criteria to determine when patients require treatment. In fact, when I first see patients in clinic, I tell them about the GELF criteria, so they’re actually following along with me when we’re looking at scans together and following their blood counts; they understand when we’re getting close to needing treatment.

Then, once they have treatment, I often think about other factors when I’m initiating a second or third line; that may become how long their first remission lasted; how it presents, either as a large bulky disease or a low-volume disease; and how the patient feels about the relapse. For example, if I have a patient who receives induction chemotherapy with Rituxan (rituximab) and they go 8 years, I’m probably not going to do chemotherapy again. I’ll just give them more Rituxan because they’ve shown to me that they’re a very low-risk patient. I might use that Rituxan earlier, even before they have progression of disease or symptoms—again, because I get the sense that I can control them with not a lot of therapy. I do think that I use the GELF as a hard fast, so if they have symptoms, I’m not going to watch and wait with patients in the relapsed setting. But I guess what I’m saying is I may treat patients a little earlier, before they actually develop GELF criteria in the relapsed setting, depending on how long their remission is.

Joshua Brody, MD: It’s rare that they’ll have better kinetics on their recurrence than they had in their initial presentation. If they quickly progressed needing more therapy the first time around, you can see that it’s going to happen again.

Nathan H. Fowler, MD: As we’ve seen from data, the patients that go at least 2 years, they’re probably never going to die of their disease. That’s really nice, because what that tells me is, most of the patients had very heterogenous therapy in the second and third line, but despite that, their survivals all were very, very good long term.

Matthew Lunning, DO: So, do you stop doing surveillance imaging, is the question. I think about it as, if we’re not doing surveillance imaging, are you capturing their relapse on physical exam or some laboratory finding, or a complaint that prompts a scan, versus doing active surveillance in a symptomatic individual and capturing borderline GELF criteria? You don’t then know the velocity of that change. I think that that’s an important piece. If you’re not doing scans, you may acknowledge that you have nodes that are growing, but you feel well. Maybe we look again, and to your point, if it’s after 2 years after their first line of therapy, then that might be a slow relapser, and it may have been relapsing for a very long time.

John P. Leonard, MD: I would suspect, that with someone who has a known history of follicular lymphoma, that the burden of disease they present with at relapse—and I clinically detect the relapse—is probably lower than when they were diagnosed in general. Because you’re seeing them, you’re examining their nodes, they’re more attentive, et cetera. Even in the absence of scans, I think that the first relapse tends to be diagnosed earlier. The exception may be transformation—when the patient will come in with a bulky mass or rapid progression. But I think either way, if your approach is to use more minimal treatment or to take your time with a first relapsed patient, you’re probably going to find those at a state where the patient has less disease going on.

Sonali M. Smith, MD: The challenge that I’m having is that, first of all, this whole early progression of disease is something that we are just now aware of. Sometimes you’ll have somebody who progresses early, but they don’t actually need treatment. So, you know their prognosis is not going to be great, but it’s not really clear that you need to intervene at that time. I think that’ll be the next generation of questions.

Ian W. Flinn, MD, PhD: It’s probably an important one. The other thing that you bring up here in this discussion about scans; we live in this era where everyone says to do less scans. Of course, they’re not without harm, scans. At the same time, you can’t really tell if someone progresses unless they get very symptomatic. Have you changed how often you do scans or if you do scans?

Sonali M. Smith, MD: I try very hard not to do scans unless somebody has symptoms, change in blood work, or a change in exam. I think, again, I’ve just started to really take the long view. You look at some of these long-term data sets and know that they’re going to be alive 10, 15, maybe 20 years later. So, I try very hard. Unless they’re part of some particularly high-risk background, I try not to do the scans.

Ian W. Flinn, MD, PhD: Nathan, does that matter how far out you are from therapy? The first 2 years versus 5 years?

Nathan H. Fowler, MD: Yes, so I may be an outlier in the group. I am still a believer in imaging. I think that regarding what you mentioned earlier, I tend to do more intense imaging in the first year because, again, I’m thinking about transformation. Am I missing an occult transformation? Generally, I’ll do a scan about 3 months after they finish their first therapy and then 3 to 6 months again. Very quickly I start moving to annual imaging if I’m kind of ruling out any aggressive course. As you mentioned, if they have a fairly long remission—in other words, you’re talking 2 or 3 years—we start really reducing imaging, and often in patients who are several years out, all they’re getting, for example, is a chest x-ray, blood work, and physical exam.

Ian W. Flinn, MD, PhD: This is all CT scans. Do you do a PET scan after therapy at all?

Nathan H. Fowler, MD: In the United States…and I’ll just say that imaging often is dictated by insurance companies, so I think PET imaging is actually a much better modality for following a follicular lymphoma patient. When I’m talking about PET, I’m talking about a PET-CT. Current PET-CTs have essentially the same amount of radiation as a standard CT. So, again, I think that if I was to follow a patient and I could do whatever I wanted, I would probably use PET-CTs in patients; but CT scans are currently what’s approved.

Transcript Edited for Clarity 
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