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Immunochemotherapy Approaches for 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: Nathan, there are a number of different choices that we have—and we’ll get into some of this in a second—for frontline therapy for patients with follicular lymphoma, but not all patients are the same. Some are older, some are young, or some have heart disease; some have other issues. What factors make you want to use one therapy versus another?

Nathan H. Fowler, MD: The difficult thing in untreated follicular lymphoma is that many things work. So, when you’re looking at options, this isn’t going to be about whether a patient responds or not. It’s about the toxicities, as you mentioned, that are associated with each individual regimen.

If you think about just a garden variety low-grade lymphoma patient who’s not transformed, the common options in the United States would be really CHOP or bendamustine with rituximab. I think CVP less and less. I tend to have used bendamustine in most patients, unless they have some comorbid condition—for example, heart disease—or they have some underlying peripheral neuropathy. I’m worried about vincristine. But for the garden variety patient, I tend to pick bendamustine in the majority of cases.

That’s really because I think most of the data from a couple of different trials have suggested that bendamustine and CHOP probably are fairly equivalent with regards to controlling the disease long-term. So, again, I don’t really look much at the tumor burden, etc, when I’m deciding on different treatment options. It’s more about the comorbidities that the patient has.
 
Ian W. Flinn, MD, PhD: John, I think this question of R-CHOP versus rituximab/bendamustine, I figure with a few clinical trials that would have answered most people’s questions. But it’s still very controversial. Different people do different things. What do you do?

John P. Leonard, MD: Well, I tend to similarly, but perhaps a little different, put patients in the 3 main kinds of categories: those that I would give single-agent rituximab to, those that I would use BR [in], and those that I would use R-CHOP for. We talked about the R-CHOP group already, the group that has concern for transformation in particular. So, rituximab alone versus rituximab-bendamustine. It’s nice for patients that they can make a choice and you’re not compromising their long-term outcome. It’s clear that 2 drugs are better than 1, as far as efficacy. It’s clear that 2 drugs are more toxic than 1, as far as safety.

But at the end of the day, I don’t know that we have any long-term data that suggest if you start with BR versus starting with R, and then use BR perhaps later, that is a difference. So, there are physicians who have had a number of patients who’ve had rituximab as a single agent and have gone 5 or 10 years not needing treatment. Now those tend not to be patients with a lot of bulky disease, but certainly, if somebody’s going to watch and wait for a while—they have cosmetic issues, they have nodes that are 2 cm or 3 cm but have indication for treatment—those are people where I think Rituxan alone is a reasonable option. But, again, it’s a tradeoff and the patient can choose.

I probably use a little more single-agent rituximab than Nathan at least described, but I think there’s not a wrong answer. A month of treatment, if you can have a meaningful remission for a period of time, as long as you know that you may be needing treatment again in another year or two, or you may get lucky and go longer, I think that’s a reasonable choice for patients to make. But I tend to use more single-agent rituximab in people whom I’ve watched and waited for a while, and they are now just crossing the threshold in that regard.

Ian W. Flinn, MD, PhD: Josh, there’s this new preparation of rituximab that’s given subcutaneously; it’s much quicker, it’s just 10 minutes versus 90 minutes or more for an infusion. Are you using it? Do you use it for everybody? Do you use it just for select patients? Tell me about it.

Joshua Brody, MD: Yes, that’s a good question. This subcutaneous rituximab with hyaluronidase is quicker, as you say. Just to clarify; all patients still have to go through their first dose of IV, a standard slow titration of rate of infusion to see that patients tolerate well. The patients that have really protracted infusions because of infusion reactions, we do not switch them over to subcutaneous rituximab because we want to be able to watch them more closely and make sure that they tolerate their second dose as well. Those are the same patients we all know who have infusion reactions, the high–tumor burden patients. For the patients who tolerate well, and we migrate some of them over, they just started using it recently. It was a matter of accessibility, of having it on our formulary, of getting reimbursed easily—all practical things.

For those patients, yes, a quick injection rather than a variable-duration infusion. We have some places where we’re comfortable doing 90-minute infusions; patients who have tolerated it well in the past. Literally, some of the less familiar oncology floors still do 4-hour infusions. So, yes, quick injection for the patient is very well tolerated in general. Some of these local injection-site reactions, really low-grade, not so bad. For the patient who is coming by to get their rituximab, on the way home from work or something, that makes a difference between being able to do it on a weekday or having to take your Saturday to do it. So, we’ve had good tolerability and a good experience with it overall.

Ian W. Flinn, MD, PhD: Matt, the same in your institution, and specifically, is there any population that you treat with rituximab, other than the people who are having infusion reactions, who you wouldn’t use it on?

Matthew Lunning, DO: Well, I think it’s very interesting in that. It makes sense that the NCCN guidelines would have put the footnote to allow it in other diseases, like marginal zone lymphoma or mantle cell lymphoma, where it wasn’t necessarily studied, as well. So, I think I would classify us as early adopters with the subcutaneous, because our pharmacy put it in and we had to make a choice. Rituximab disappeared, and you have to choose. Are you going to continue to give subcutaneous or are you going to give IV?
We had to have the conversation. It comes down to another thing, spending more time and describing the differences. To Josh’s point, if I have that person that has had infusion-related reactions in the past, or uncharacteristic timing of infusions, or weird things happening with the rituximab, I’m going to stick to the IV because it’s tried and true. But to those people who want to spend less time and want to take less time off of work to get the rituximab, a half-a-days’ vacation saved is well worth it, I think, for a poke in the belly and some soreness for a couple of days. So, I’ve had discussions, and I’ve seen it both sides where people come back and say, “I’ll take the IV back,” or, “I’m comfortable with the subcutaneous moving forward.”

Joshua Brody, MD: It’s not just better for the patients, but we sometimes cannot book patients cause the chairs are so full; getting the patient in and out of there in 25 minutes.

Matthew Lunning, DO: Right. I need that chair for the first-dose rituximab patient who has an aggressive large-cell lymphoma. I agree with you.

Transcript Edited for Clarity 

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Transcript: 

Ian W. Flinn, MD, PhD: Nathan, there are a number of different choices that we have—and we’ll get into some of this in a second—for frontline therapy for patients with follicular lymphoma, but not all patients are the same. Some are older, some are young, or some have heart disease; some have other issues. What factors make you want to use one therapy versus another?

Nathan H. Fowler, MD: The difficult thing in untreated follicular lymphoma is that many things work. So, when you’re looking at options, this isn’t going to be about whether a patient responds or not. It’s about the toxicities, as you mentioned, that are associated with each individual regimen.

If you think about just a garden variety low-grade lymphoma patient who’s not transformed, the common options in the United States would be really CHOP or bendamustine with rituximab. I think CVP less and less. I tend to have used bendamustine in most patients, unless they have some comorbid condition—for example, heart disease—or they have some underlying peripheral neuropathy. I’m worried about vincristine. But for the garden variety patient, I tend to pick bendamustine in the majority of cases.

That’s really because I think most of the data from a couple of different trials have suggested that bendamustine and CHOP probably are fairly equivalent with regards to controlling the disease long-term. So, again, I don’t really look much at the tumor burden, etc, when I’m deciding on different treatment options. It’s more about the comorbidities that the patient has.
 
Ian W. Flinn, MD, PhD: John, I think this question of R-CHOP versus rituximab/bendamustine, I figure with a few clinical trials that would have answered most people’s questions. But it’s still very controversial. Different people do different things. What do you do?

John P. Leonard, MD: Well, I tend to similarly, but perhaps a little different, put patients in the 3 main kinds of categories: those that I would give single-agent rituximab to, those that I would use BR [in], and those that I would use R-CHOP for. We talked about the R-CHOP group already, the group that has concern for transformation in particular. So, rituximab alone versus rituximab-bendamustine. It’s nice for patients that they can make a choice and you’re not compromising their long-term outcome. It’s clear that 2 drugs are better than 1, as far as efficacy. It’s clear that 2 drugs are more toxic than 1, as far as safety.

But at the end of the day, I don’t know that we have any long-term data that suggest if you start with BR versus starting with R, and then use BR perhaps later, that is a difference. So, there are physicians who have had a number of patients who’ve had rituximab as a single agent and have gone 5 or 10 years not needing treatment. Now those tend not to be patients with a lot of bulky disease, but certainly, if somebody’s going to watch and wait for a while—they have cosmetic issues, they have nodes that are 2 cm or 3 cm but have indication for treatment—those are people where I think Rituxan alone is a reasonable option. But, again, it’s a tradeoff and the patient can choose.

I probably use a little more single-agent rituximab than Nathan at least described, but I think there’s not a wrong answer. A month of treatment, if you can have a meaningful remission for a period of time, as long as you know that you may be needing treatment again in another year or two, or you may get lucky and go longer, I think that’s a reasonable choice for patients to make. But I tend to use more single-agent rituximab in people whom I’ve watched and waited for a while, and they are now just crossing the threshold in that regard.

Ian W. Flinn, MD, PhD: Josh, there’s this new preparation of rituximab that’s given subcutaneously; it’s much quicker, it’s just 10 minutes versus 90 minutes or more for an infusion. Are you using it? Do you use it for everybody? Do you use it just for select patients? Tell me about it.

Joshua Brody, MD: Yes, that’s a good question. This subcutaneous rituximab with hyaluronidase is quicker, as you say. Just to clarify; all patients still have to go through their first dose of IV, a standard slow titration of rate of infusion to see that patients tolerate well. The patients that have really protracted infusions because of infusion reactions, we do not switch them over to subcutaneous rituximab because we want to be able to watch them more closely and make sure that they tolerate their second dose as well. Those are the same patients we all know who have infusion reactions, the high–tumor burden patients. For the patients who tolerate well, and we migrate some of them over, they just started using it recently. It was a matter of accessibility, of having it on our formulary, of getting reimbursed easily—all practical things.

For those patients, yes, a quick injection rather than a variable-duration infusion. We have some places where we’re comfortable doing 90-minute infusions; patients who have tolerated it well in the past. Literally, some of the less familiar oncology floors still do 4-hour infusions. So, yes, quick injection for the patient is very well tolerated in general. Some of these local injection-site reactions, really low-grade, not so bad. For the patient who is coming by to get their rituximab, on the way home from work or something, that makes a difference between being able to do it on a weekday or having to take your Saturday to do it. So, we’ve had good tolerability and a good experience with it overall.

Ian W. Flinn, MD, PhD: Matt, the same in your institution, and specifically, is there any population that you treat with rituximab, other than the people who are having infusion reactions, who you wouldn’t use it on?

Matthew Lunning, DO: Well, I think it’s very interesting in that. It makes sense that the NCCN guidelines would have put the footnote to allow it in other diseases, like marginal zone lymphoma or mantle cell lymphoma, where it wasn’t necessarily studied, as well. So, I think I would classify us as early adopters with the subcutaneous, because our pharmacy put it in and we had to make a choice. Rituximab disappeared, and you have to choose. Are you going to continue to give subcutaneous or are you going to give IV?
We had to have the conversation. It comes down to another thing, spending more time and describing the differences. To Josh’s point, if I have that person that has had infusion-related reactions in the past, or uncharacteristic timing of infusions, or weird things happening with the rituximab, I’m going to stick to the IV because it’s tried and true. But to those people who want to spend less time and want to take less time off of work to get the rituximab, a half-a-days’ vacation saved is well worth it, I think, for a poke in the belly and some soreness for a couple of days. So, I’ve had discussions, and I’ve seen it both sides where people come back and say, “I’ll take the IV back,” or, “I’m comfortable with the subcutaneous moving forward.”

Joshua Brody, MD: It’s not just better for the patients, but we sometimes cannot book patients cause the chairs are so full; getting the patient in and out of there in 25 minutes.

Matthew Lunning, DO: Right. I need that chair for the first-dose rituximab patient who has an aggressive large-cell lymphoma. I agree with you.

Transcript Edited for Clarity 
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