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Follicular Lymphoma: Outcomes with Immunotherapy

Panelists:Bruce Cheson, MD, Georgetown Lombardi Comprehensive Cancer Center; Nathan Fowler, MD, The University of Texas MD Anderson Cancer Center; Anas Younes, MD, Memorial Sloan Kettering Cancer Center
Published Online: Saturday, Oct 28, 2017

Transcript: 

Bruce Cheson, MD: Welcome to this OncLive News Network® presentation broadcasting live from MJH Studios. Today’s discussion will be focused on “Recent Advances in Treating Follicular Lymphoma.” I’m your host, Dr. Bruce Cheson, professor of medicine and head of hematology and cellular therapy at the Georgetown University Hospital, Lombardi Comprehensive Cancer Center in Washington, DC. Today I am joined by 2 of my colleagues, and friends, who are renowned experts in the treatment of lymphoma.

Anas Younes, MD: Hi, I’m Dr. Anas Younes, chief of lymphoma service at Memorial Sloan Kettering Cancer Center, and I’m happy to be here.

Nathan Fowler, MD: And I’m Nathan Fowler, associate professor of medicine at the University of Texas MD Anderson Cancer Center in Houston.

Bruce Cheson, MD: We’re going to spend the next 60 minutes talking about an area that has seen significant progress recently: the treatment of follicular lymphoma. We’ll discuss how the latest data from clinical trials are shaping the way you will treat your patients. At the end of the program, we will open the discussion to answer questions that were submitted to OncLive® in advance from our viewers.
Now, what we’ve all seen, since we treat a lot of follicular lymphomas, is that not all patients are created equal. They seem to show up with similar clinical features and have remarkably different outcomes. There have been a number of attempts to develop prognostic scores to separate these patients into clinically meaningful groups that we approach differently with regard to our therapy. Have we really accomplished that?

Nathan Fowler, MD: It’s tough. When patients first present to your clinic, we do the typical things. We do staging, and we figure out what the grade of the lymphoma is. Then we often have a discussion about what the first steps are in managing the patient. As you mentioned, because many patients present differently and they can have these very different outcomes with the same therapy, it’s a little bit difficult. So, I often do use some of the new scoring systems—FLIPI-2, m7-FLIPI—and these are systems that look at patients’ pretreatment and patient characteristics, things like age, stage, LDH [Lactate dehydrogenase], etc. It can give us a sense of how patients might do in the long term. Ultimately, I don’t necessarily base treatment decisions on those different scoring systems, but it does give me a gestalt about how these patients are going to do over the long term.

Bruce Cheson, MD: Anas, what about the more molecular prognostic systems like the m7-FLIPI?

Anas Younes, MD: The m7-FLIPI system uses 7 gene signatures to predict the outcome of patients treated with frontline regimens. Unfortunately, it doesn’t guide therapy. It doesn’t tell us how to treat these patients, it just tells us about long-term outcomes. We don’t have a prognostic factor model based on genetics or biologic features that would guide therapy at the present time.

Bruce Cheson, MD: So, we treat our patients based on how we treat our patients, not on any scoring systems. But after treatment, something strange happens. You’ve got 2 basic groups of patients. You’ve got those who have an event within 1 year, 2 years, or 30 months, but patients do great if they don’t; if they do have that event, they do very poorly. How can you approach that observation in the management of these patients?

Nathan Fowler, MD: That’s tough. What you’re referring to, obviously, Bruce, are those data that have come out fairly recently looking at patients who progress early after front-line therapy. We now have 2—well, actually, there are several—groups that have presented data showing that patients who progress after CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisolone], as well as after some of the other newer combined chemoimmunotherapy regimens, tend to do worse if they progress early. Very similar to the FLIPI and the m7-FLIPI scoring systems, although we have these data, I don’t think it’s really clear how we’re going to use these data.

What I mean by that is, although these patients tend to do worse, it’s unclear whether changing intervention when they relapse is going to change that outcome or not. It may be that these patients, unfortunately, have certain biological characteristics that are going to portend a poor prognosis, and that will still be poor even with newer agents.
Now, I think all of us hope that’s not the truth, and there are a lot of newer trials coming out where we’re looking at using novel agents for these patients who progress early. But at least today, I think if I have a patient who progresses within the first 2 years, I still go through the same decision process. That means picking another chemotherapy that is different than their first-line treatment.

Bruce Cheson, MD: What you’re saying is, we’ve got to wait 2 years and see what happens.

Nathan Fowler, MD: Right.

Bruce Cheson, MD: We have a number of ways to predict outcomes earlier, such as PET scans or MRD. Do you use those to judge and guide how you manage your patients?

Anas Younes, MD: MRD, first, is really not used in clinical practice outside of clinical research to guide therapy. We are incorporating multiple assays to measure circulating tumor DNA and call it MRD, in a setup of different treatment strategies, but we’re not acting on it yet. We’re just collecting this information.
The PET scan is also after the event. You already started therapy, so whether you are talking about interim PET scans or end of therapy PET scans, yes, they can tell you how the disease will behave. But you’re still not picking up on these patients up front. So, yes, we use PET imaging, and it’s a very good tool to tell you what the outcome’s going to be, but we need some tools or algorithms or guidelines to pick up on these patients up front and offer them different therapy if possible.

Bruce Cheson, MD: There has been an observation by Michel Meignan’s coworkers of combining total metabolic tumor volume with the FLIPI-2 system. Before treatment, you can separate patients into 3 distinct groups. Is that ready for prime time?

Anas Younes, MD: I don’t think it’s ready, yet, for prime time. The data need to be confirmed, need to be transferable so an average community oncologist knows how to deal with it, interpret it, and then use it. Right now, I think it’s a great observation. I think it’s a good research tool. Whether this will become a part of a standard practice is yet to be determined.

Bruce Cheson, MD: Did you want to make any more comments, Nathan?

Nathan Fowler, MD: No, I totally agree with Anas. One of the problems I have with a lot of the scoring systems, whether that’s using the m7-FLIPI score or total metabolic volume or the FLIPI score and NTIs [nonthyroidal illnesses], they only predict how a group of patients will do. If you look at individual patients within that—for example, individual patients who are in the m7-FLIPI group—a significant portion of them will actually do greatly, and do greatly long term.

When I’m faced with talking to a patient about the scoring system, especially patients who have a poor score, I like to remind that this is not universal. Some patients will do well, even with these scoring systems. Again, that’s relevant when we’re thinking about how to design next-line regimens and maybe put patients in different groups. At least with the scoring systems we have today, because they’re not universal, I have a hard time picking treatment or putting patients on a certain trial based upon the available scoring systems.

Bruce Cheson, MD: I think we all agree that that’s the holy grail right now, predicting patients upfront—not groups, but individual patients—and stratifying them based on some sort of biomarker as to what kind of therapy they’d respond to versus another.

Transcript Edited for Clarity 
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Transcript: 

Bruce Cheson, MD: Welcome to this OncLive News Network® presentation broadcasting live from MJH Studios. Today’s discussion will be focused on “Recent Advances in Treating Follicular Lymphoma.” I’m your host, Dr. Bruce Cheson, professor of medicine and head of hematology and cellular therapy at the Georgetown University Hospital, Lombardi Comprehensive Cancer Center in Washington, DC. Today I am joined by 2 of my colleagues, and friends, who are renowned experts in the treatment of lymphoma.

Anas Younes, MD: Hi, I’m Dr. Anas Younes, chief of lymphoma service at Memorial Sloan Kettering Cancer Center, and I’m happy to be here.

Nathan Fowler, MD: And I’m Nathan Fowler, associate professor of medicine at the University of Texas MD Anderson Cancer Center in Houston.

Bruce Cheson, MD: We’re going to spend the next 60 minutes talking about an area that has seen significant progress recently: the treatment of follicular lymphoma. We’ll discuss how the latest data from clinical trials are shaping the way you will treat your patients. At the end of the program, we will open the discussion to answer questions that were submitted to OncLive® in advance from our viewers.
Now, what we’ve all seen, since we treat a lot of follicular lymphomas, is that not all patients are created equal. They seem to show up with similar clinical features and have remarkably different outcomes. There have been a number of attempts to develop prognostic scores to separate these patients into clinically meaningful groups that we approach differently with regard to our therapy. Have we really accomplished that?

Nathan Fowler, MD: It’s tough. When patients first present to your clinic, we do the typical things. We do staging, and we figure out what the grade of the lymphoma is. Then we often have a discussion about what the first steps are in managing the patient. As you mentioned, because many patients present differently and they can have these very different outcomes with the same therapy, it’s a little bit difficult. So, I often do use some of the new scoring systems—FLIPI-2, m7-FLIPI—and these are systems that look at patients’ pretreatment and patient characteristics, things like age, stage, LDH [Lactate dehydrogenase], etc. It can give us a sense of how patients might do in the long term. Ultimately, I don’t necessarily base treatment decisions on those different scoring systems, but it does give me a gestalt about how these patients are going to do over the long term.

Bruce Cheson, MD: Anas, what about the more molecular prognostic systems like the m7-FLIPI?

Anas Younes, MD: The m7-FLIPI system uses 7 gene signatures to predict the outcome of patients treated with frontline regimens. Unfortunately, it doesn’t guide therapy. It doesn’t tell us how to treat these patients, it just tells us about long-term outcomes. We don’t have a prognostic factor model based on genetics or biologic features that would guide therapy at the present time.

Bruce Cheson, MD: So, we treat our patients based on how we treat our patients, not on any scoring systems. But after treatment, something strange happens. You’ve got 2 basic groups of patients. You’ve got those who have an event within 1 year, 2 years, or 30 months, but patients do great if they don’t; if they do have that event, they do very poorly. How can you approach that observation in the management of these patients?

Nathan Fowler, MD: That’s tough. What you’re referring to, obviously, Bruce, are those data that have come out fairly recently looking at patients who progress early after front-line therapy. We now have 2—well, actually, there are several—groups that have presented data showing that patients who progress after CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisolone], as well as after some of the other newer combined chemoimmunotherapy regimens, tend to do worse if they progress early. Very similar to the FLIPI and the m7-FLIPI scoring systems, although we have these data, I don’t think it’s really clear how we’re going to use these data.

What I mean by that is, although these patients tend to do worse, it’s unclear whether changing intervention when they relapse is going to change that outcome or not. It may be that these patients, unfortunately, have certain biological characteristics that are going to portend a poor prognosis, and that will still be poor even with newer agents.
Now, I think all of us hope that’s not the truth, and there are a lot of newer trials coming out where we’re looking at using novel agents for these patients who progress early. But at least today, I think if I have a patient who progresses within the first 2 years, I still go through the same decision process. That means picking another chemotherapy that is different than their first-line treatment.

Bruce Cheson, MD: What you’re saying is, we’ve got to wait 2 years and see what happens.

Nathan Fowler, MD: Right.

Bruce Cheson, MD: We have a number of ways to predict outcomes earlier, such as PET scans or MRD. Do you use those to judge and guide how you manage your patients?

Anas Younes, MD: MRD, first, is really not used in clinical practice outside of clinical research to guide therapy. We are incorporating multiple assays to measure circulating tumor DNA and call it MRD, in a setup of different treatment strategies, but we’re not acting on it yet. We’re just collecting this information.
The PET scan is also after the event. You already started therapy, so whether you are talking about interim PET scans or end of therapy PET scans, yes, they can tell you how the disease will behave. But you’re still not picking up on these patients up front. So, yes, we use PET imaging, and it’s a very good tool to tell you what the outcome’s going to be, but we need some tools or algorithms or guidelines to pick up on these patients up front and offer them different therapy if possible.

Bruce Cheson, MD: There has been an observation by Michel Meignan’s coworkers of combining total metabolic tumor volume with the FLIPI-2 system. Before treatment, you can separate patients into 3 distinct groups. Is that ready for prime time?

Anas Younes, MD: I don’t think it’s ready, yet, for prime time. The data need to be confirmed, need to be transferable so an average community oncologist knows how to deal with it, interpret it, and then use it. Right now, I think it’s a great observation. I think it’s a good research tool. Whether this will become a part of a standard practice is yet to be determined.

Bruce Cheson, MD: Did you want to make any more comments, Nathan?

Nathan Fowler, MD: No, I totally agree with Anas. One of the problems I have with a lot of the scoring systems, whether that’s using the m7-FLIPI score or total metabolic volume or the FLIPI score and NTIs [nonthyroidal illnesses], they only predict how a group of patients will do. If you look at individual patients within that—for example, individual patients who are in the m7-FLIPI group—a significant portion of them will actually do greatly, and do greatly long term.

When I’m faced with talking to a patient about the scoring system, especially patients who have a poor score, I like to remind that this is not universal. Some patients will do well, even with these scoring systems. Again, that’s relevant when we’re thinking about how to design next-line regimens and maybe put patients in different groups. At least with the scoring systems we have today, because they’re not universal, I have a hard time picking treatment or putting patients on a certain trial based upon the available scoring systems.

Bruce Cheson, MD: I think we all agree that that’s the holy grail right now, predicting patients upfront—not groups, but individual patients—and stratifying them based on some sort of biomarker as to what kind of therapy they’d respond to versus another.

Transcript Edited for Clarity 
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