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Risk Classification and Assessment 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: Tuesday, Jul 24, 2018



Transcript: 

Ian W. Flinn, MD, PhD: Let’s talk about risk stratification, Matt. There are a bunch of different scales that you can use, the FLIPI, the FLIPI2. Do you use these? Is it just for research? Does it help you in any way?

Matthew Lunning, DO: Yes. I go back to thinking about the mannequins for the FLIPI and counting nodal stations—which, as a Fellow, it’s a project that you often got to do—and you had to add them up and figure out what their FLIPI score is or their FLIPI2 score. Then coming along, as we’ve ventured further and further into the rituximab era, the m7-FLIPI. But the m7-FLIPI incorporates some tests that may not be available to everybody.

The utility of that, stepping back, while it was interesting data, and in some ways created some controversy around the FLIPI and the FLIPI2, I just don’t know how applicable the m7-FLIPI is. I put it down because I was once doing retrospective studies and trying to help the next person going through to say this was their FLIPI score at diagnosis, so somebody else isn’t going to have to scour through documents to do it. Do it once, do it right. But to say that it affects how I’m going to treat a patient, versus active surveillance, or guiding me along as a risk adaptation strategy, it’s not to date.

Sonali M. Smith, MD: Part of the challenge is that people confuse the FLIPI with the need to treat. That’s something just to look out for, in the sense that somebody can have a very high FLIPI, but if they’re asymptomatic, there’s still no indication to expose them to treatment that, so far, hasn’t shown to cure anyone or extend their life.

Nathan H. Fowler, MD: Right. Certainly, what you’re talking about exposes one, and probably the main, weakness within these scoring systems, which is that it doesn’t predict individual patient risk. It predicts the group’s risk, but there are many patients, as you mentioned, who have high-risk FLIPI scores. They have very-low-volume disease and may do very, very well. And there are patients with very-low-risk FLIPI scores who sometimes do poorly. Using it to stratify treatment is, I think, pretty difficult.

John P. Leonard, MD: On the flip side, pardon the pun, I think that the patients who are high-risk FLIPI patients are the ones who tend to have more disease, tend to have more symptoms, may be anemic. And so, at the end of the day, I agree with you that if a patient has high-risk FLIPI and still feels fine, and doesn’t have indications for treatment, it’s fine not to treat them. But when you look at the Venn diagram, a larger proportion of higher-risk FLIPI patients are going to have an indication for treatment than the lower-risk FLIP patients will.

Ian W. Flinn, MD, PhD: Do you give a different therapy? Do you give R-CHOP versus bendamustine or does it not make any difference to you?

John P. Leonard, MD: I would say that it doesn’t strictly make a difference, but again, remembering that number of sites and disease and LDH fall into the FLIPI category, and so many of those patients will have bulkier disease, that’s where I’m at least looking more closely. You have to figure that the high-risk FLIPI group, if any of the groups has a possibility of occult transformation, that’s going to be the group that has it. I would tend to look a little harder for transformation or think a little harder for transformation in that group. If I found it, obviously I’d give R-CHOP.

Ian W. Flinn, MD, PhD: Sonali, you mentioned that the FLIPI wasn’t necessarily an indication for treatment. What are the indications for treatment? We have the GELF criteria. What drives you to want to treat somebody?

Sonali M. Smith, MD: I think the key thing to remember is that, this is a disease that, to date, we can’t cure. The goal of treatment is essentially palliation and trying to give people a deep remission that lasts. Until they have symptoms, I have nothing to palliate, so I wait until they have symptoms. There’s the GELF criteria and there’s also BNLI criteria and NCCN has their criteria, but they all fall along the same lines, which is, if their cytopenia is due to disease, if there’s effusions due to disease or other B symptoms related to the lymphoma, then you’re justified in starting some type of therapy.

Now, there are times when people don’t meet the GELF criteria that I will think about therapy and sometimes that’s very patient driven. Either they feel extremely uncomfortable with the observational approach—active observation is the term I’m using now instead of watch and wait. I think active surveillance and active observation sounds better—for those patients, there is still a need to take care of the whole patient. So, if they do want something, I’m trying to find something low intensity. But for most patients, I wait until they have some type of GELF criteria, which is symptoms, effusions, or cytopenia.

Transcript Edited for Clarity 

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Transcript: 

Ian W. Flinn, MD, PhD: Let’s talk about risk stratification, Matt. There are a bunch of different scales that you can use, the FLIPI, the FLIPI2. Do you use these? Is it just for research? Does it help you in any way?

Matthew Lunning, DO: Yes. I go back to thinking about the mannequins for the FLIPI and counting nodal stations—which, as a Fellow, it’s a project that you often got to do—and you had to add them up and figure out what their FLIPI score is or their FLIPI2 score. Then coming along, as we’ve ventured further and further into the rituximab era, the m7-FLIPI. But the m7-FLIPI incorporates some tests that may not be available to everybody.

The utility of that, stepping back, while it was interesting data, and in some ways created some controversy around the FLIPI and the FLIPI2, I just don’t know how applicable the m7-FLIPI is. I put it down because I was once doing retrospective studies and trying to help the next person going through to say this was their FLIPI score at diagnosis, so somebody else isn’t going to have to scour through documents to do it. Do it once, do it right. But to say that it affects how I’m going to treat a patient, versus active surveillance, or guiding me along as a risk adaptation strategy, it’s not to date.

Sonali M. Smith, MD: Part of the challenge is that people confuse the FLIPI with the need to treat. That’s something just to look out for, in the sense that somebody can have a very high FLIPI, but if they’re asymptomatic, there’s still no indication to expose them to treatment that, so far, hasn’t shown to cure anyone or extend their life.

Nathan H. Fowler, MD: Right. Certainly, what you’re talking about exposes one, and probably the main, weakness within these scoring systems, which is that it doesn’t predict individual patient risk. It predicts the group’s risk, but there are many patients, as you mentioned, who have high-risk FLIPI scores. They have very-low-volume disease and may do very, very well. And there are patients with very-low-risk FLIPI scores who sometimes do poorly. Using it to stratify treatment is, I think, pretty difficult.

John P. Leonard, MD: On the flip side, pardon the pun, I think that the patients who are high-risk FLIPI patients are the ones who tend to have more disease, tend to have more symptoms, may be anemic. And so, at the end of the day, I agree with you that if a patient has high-risk FLIPI and still feels fine, and doesn’t have indications for treatment, it’s fine not to treat them. But when you look at the Venn diagram, a larger proportion of higher-risk FLIPI patients are going to have an indication for treatment than the lower-risk FLIP patients will.

Ian W. Flinn, MD, PhD: Do you give a different therapy? Do you give R-CHOP versus bendamustine or does it not make any difference to you?

John P. Leonard, MD: I would say that it doesn’t strictly make a difference, but again, remembering that number of sites and disease and LDH fall into the FLIPI category, and so many of those patients will have bulkier disease, that’s where I’m at least looking more closely. You have to figure that the high-risk FLIPI group, if any of the groups has a possibility of occult transformation, that’s going to be the group that has it. I would tend to look a little harder for transformation or think a little harder for transformation in that group. If I found it, obviously I’d give R-CHOP.

Ian W. Flinn, MD, PhD: Sonali, you mentioned that the FLIPI wasn’t necessarily an indication for treatment. What are the indications for treatment? We have the GELF criteria. What drives you to want to treat somebody?

Sonali M. Smith, MD: I think the key thing to remember is that, this is a disease that, to date, we can’t cure. The goal of treatment is essentially palliation and trying to give people a deep remission that lasts. Until they have symptoms, I have nothing to palliate, so I wait until they have symptoms. There’s the GELF criteria and there’s also BNLI criteria and NCCN has their criteria, but they all fall along the same lines, which is, if their cytopenia is due to disease, if there’s effusions due to disease or other B symptoms related to the lymphoma, then you’re justified in starting some type of therapy.

Now, there are times when people don’t meet the GELF criteria that I will think about therapy and sometimes that’s very patient driven. Either they feel extremely uncomfortable with the observational approach—active observation is the term I’m using now instead of watch and wait. I think active surveillance and active observation sounds better—for those patients, there is still a need to take care of the whole patient. So, if they do want something, I’m trying to find something low intensity. But for most patients, I wait until they have some type of GELF criteria, which is symptoms, effusions, or cytopenia.

Transcript Edited for Clarity 
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