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Follicular Lymphoma: Progression of Disease

Panelists: Ian W. Flinn, MD, PhD, Sarah Cannon Research Institute; Matthew Lunning, DO, University of Nebraska Medical Center; John M. Pagel, MD, PhD, Swedish Cancer Institute; Pier Luigi Zinzani, MD, PhD, University of Bologna
Published: Thursday, Aug 22, 2019



Transcript: 

Ian W. Flinn, MD, PhD: We’re going to move on now and talk about the relapsed-refractory patients. Who’s the highest risk for relapsing? Do we know that, Matt, or do we know only it after it happens?

Matthew Lunning, DO: I truly am looking into the patient’s eyes and trying to figure out, are you going to be 1 of the 20%, or are you going to be in the 80%? And I think you know only at the end of induction how they do with response. Based on some of the data that are coming up, they have influenced me to potentially look either at the end of maintenance therapy—to say that that’s the completion or treatment No. 1—or at a 2-year endpoint from their diagnosis, or roughly around there, to see if I can capture that early progressing disease. I think the m7-FLIPI even called out that the m7-FLIPI couldn’t really look at the POD [progression of disease] of those people who are progressing within 24 months. So in all-comers, it’s hard for me to predict. It’s often why you try to have the conversation—well, maybe if you can try and shrink that population down, only in hindsight that will inform what you do in the future.

Ian W. Flinn, MD, PhD: But do we really have data? This POD 24, the earlier progressors, there is this notion that if I give people therapy and I can shrink that population, that I’m going to improve survival for people. But do we really know that? If you gave them a bone marrow transplant in frontline, you could improve POD 24, but you’re probably not going to improve overall survival for patients. John, talk to us about that a little bit.

John M. Pagel, MD, PhD: I’m not even nearly as convinced that there is such a thing as progression of disease in less than 24 months that is follicular lymphoma. I think a lot of these people probably have an underlying malignant clone that’s much more aggressive that we just haven’t seen, and it emerges early. And if we had known about that, we would have been able to treat them perhaps differently up front than wait for them to relapse within the first 2 years. But it’s clear that if you relapse early, you do worse than if you relapse late. There’s no question about that, and we worry about those people.

Who’s the highest risk then? I guess we’ve talked about this. I guess I definitely worry more about the grade 3s, and I worry about that person who came into treatment with just an unusual situation, where you’ve got that high-SUV [standardized uptake value] that doesn’t exactly fit or somebody has just really an extensive amount of disease. In particular, I worry about extranodal disease, especially in osseous involvement of other unusual sites of disease. Those are the people for whom I’m very, very worried about risk of relapse, and I’m going to pay closer attention to those patients, I think.

Matthew Lunning, DO: But I don’t think we can stray away from if we’re going to apply the POD 24. It’s been applied and informed in clinical trials right now. You can’t stray away from the original population that was studied and start to apply it to everybody with follicular lymphoma. It had to be treated with R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone], needed therapy within 6 months of diagnosis. It was a good publication, but the data [need] to be encapsulated where those patients were.

John M. Pagel, MD, PhD: And I think those people who might have done a little worse, again were probably people who had some underlying transformed clone that we just hadn’t seen yet.

Ian W. Flinn, MD, PhD: Yeah.

Pier Luigi Zinzani, MD, PhD: And this is the concept of PODs. It’s not specific for follicular lymphoma. It is also for Hodgkin lymphoma, for diffuse B-cell lymphoma. If they have it in the labs, it could be a really bad situation but not only for follicular lymphoma. The real problem that we don’t know is that it’s impossible, so far, to stratify the patient into higher risk in terms of pathobiological data and other data. We have only the...at the end of the treatment and some particular extranodal presentation. But it’s so difficult on the basis of this aspect to change the treatment at the beginning of the study.

Ian W. Flinn, MD, PhD: Maybe the real take-home message from that paper was that there’s a group of people with follicular lymphoma who are going to do well, and that’s great. We still don’t know how to treat, perhaps how to change things for the other group of patients.

Pier Luigi Zinzani, MD, PhD: And my other question for all of you, do you think it’s a real incurable disease, follicular lymphoma? Because at the end of the day, in all our patients there are some patients who continue to achieve complete response after conventional chemoimmunotherapy after more than 7, 8, 10 years. There’s a small subsets of patients by the end of the day. If you have a patient who continues complete response after more than 7, 8 years, potentially you can call this patient cured.

John M. Pagel, MD, PhD: Well, we all have a patient that we can think of, and I’m sure the audience does too where you treated their follicular lymphoma and they never relapse. It does happen. Unfortunately, it’s pretty uncommon, right?

Matthew Lunning, DO: I agree.

Transcript Edited for Clarity

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Transcript: 

Ian W. Flinn, MD, PhD: We’re going to move on now and talk about the relapsed-refractory patients. Who’s the highest risk for relapsing? Do we know that, Matt, or do we know only it after it happens?

Matthew Lunning, DO: I truly am looking into the patient’s eyes and trying to figure out, are you going to be 1 of the 20%, or are you going to be in the 80%? And I think you know only at the end of induction how they do with response. Based on some of the data that are coming up, they have influenced me to potentially look either at the end of maintenance therapy—to say that that’s the completion or treatment No. 1—or at a 2-year endpoint from their diagnosis, or roughly around there, to see if I can capture that early progressing disease. I think the m7-FLIPI even called out that the m7-FLIPI couldn’t really look at the POD [progression of disease] of those people who are progressing within 24 months. So in all-comers, it’s hard for me to predict. It’s often why you try to have the conversation—well, maybe if you can try and shrink that population down, only in hindsight that will inform what you do in the future.

Ian W. Flinn, MD, PhD: But do we really have data? This POD 24, the earlier progressors, there is this notion that if I give people therapy and I can shrink that population, that I’m going to improve survival for people. But do we really know that? If you gave them a bone marrow transplant in frontline, you could improve POD 24, but you’re probably not going to improve overall survival for patients. John, talk to us about that a little bit.

John M. Pagel, MD, PhD: I’m not even nearly as convinced that there is such a thing as progression of disease in less than 24 months that is follicular lymphoma. I think a lot of these people probably have an underlying malignant clone that’s much more aggressive that we just haven’t seen, and it emerges early. And if we had known about that, we would have been able to treat them perhaps differently up front than wait for them to relapse within the first 2 years. But it’s clear that if you relapse early, you do worse than if you relapse late. There’s no question about that, and we worry about those people.

Who’s the highest risk then? I guess we’ve talked about this. I guess I definitely worry more about the grade 3s, and I worry about that person who came into treatment with just an unusual situation, where you’ve got that high-SUV [standardized uptake value] that doesn’t exactly fit or somebody has just really an extensive amount of disease. In particular, I worry about extranodal disease, especially in osseous involvement of other unusual sites of disease. Those are the people for whom I’m very, very worried about risk of relapse, and I’m going to pay closer attention to those patients, I think.

Matthew Lunning, DO: But I don’t think we can stray away from if we’re going to apply the POD 24. It’s been applied and informed in clinical trials right now. You can’t stray away from the original population that was studied and start to apply it to everybody with follicular lymphoma. It had to be treated with R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone], needed therapy within 6 months of diagnosis. It was a good publication, but the data [need] to be encapsulated where those patients were.

John M. Pagel, MD, PhD: And I think those people who might have done a little worse, again were probably people who had some underlying transformed clone that we just hadn’t seen yet.

Ian W. Flinn, MD, PhD: Yeah.

Pier Luigi Zinzani, MD, PhD: And this is the concept of PODs. It’s not specific for follicular lymphoma. It is also for Hodgkin lymphoma, for diffuse B-cell lymphoma. If they have it in the labs, it could be a really bad situation but not only for follicular lymphoma. The real problem that we don’t know is that it’s impossible, so far, to stratify the patient into higher risk in terms of pathobiological data and other data. We have only the...at the end of the treatment and some particular extranodal presentation. But it’s so difficult on the basis of this aspect to change the treatment at the beginning of the study.

Ian W. Flinn, MD, PhD: Maybe the real take-home message from that paper was that there’s a group of people with follicular lymphoma who are going to do well, and that’s great. We still don’t know how to treat, perhaps how to change things for the other group of patients.

Pier Luigi Zinzani, MD, PhD: And my other question for all of you, do you think it’s a real incurable disease, follicular lymphoma? Because at the end of the day, in all our patients there are some patients who continue to achieve complete response after conventional chemoimmunotherapy after more than 7, 8, 10 years. There’s a small subsets of patients by the end of the day. If you have a patient who continues complete response after more than 7, 8 years, potentially you can call this patient cured.

John M. Pagel, MD, PhD: Well, we all have a patient that we can think of, and I’m sure the audience does too where you treated their follicular lymphoma and they never relapse. It does happen. Unfortunately, it’s pretty uncommon, right?

Matthew Lunning, DO: I agree.

Transcript Edited for Clarity
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