Hodgkin Lymphoma News From ASH 2018: Updates From Leading Experts

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Topics include: Treatment

As part of Patient Power’s coverage from the 2018 American Society of Hematology (ASH) annual meeting, a panel of experts in Hodgkin lymphoma, including Dr. Andrew Evens, Dr. Joshua Brody, as well as Andrew and Esther Schorr, gathered to discuss the latest news and developments related to research and treatment of Hodgkin Lymphoma. These experts share their perspective on the many recent developments for treating Hodgkin lymphoma. Many new drugs have been approved in the last several months, and these specialists give us a peak into what it could mean for patients and their families. 

We thank Seattle Genetics for their support.

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Transcript

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Andrew Schorr:

Hello, and welcome to Patient Power. I’m Andrew Schorr. I’m with Esther Schorr, and we are on location in San Diego, right next to the American Society of Hematology meeting, where thousands of medical experts come from around the world to discuss the latest in blood-related conditions. If you’re watching, it’s probably because you, a loved one, or a friend has been diagnosed with Hodgkin lymphoma. Happily, there are things to talk about there that really can give encouragement to you, and we have two experts with us, and we’ll let them introduce themselves. Dr. Brody, tell us your full name, your title, and where you practice.

Dr. Brody:            

Sure. Thank you guys so much. I’m Joshua Brody. I’m the Director of the Lymphoma and Immunotherapy Program at Mt. Sinai School of Medicine in New York. We take care of patients with Hodgkin’s lymphoma, other types of lymphoma, and CLL.

Andrew Schorr:  

Okay. And, Dr. Evans.

Dr. Evans:             

Hi. Thanks again for the invitation, Andrew and Esther. It’s great to be with you. I’m Andy Evans. I’m also Director of the Lymphoma Program at Rutgers Cancer Institute of New Jersey—so, the system role, helping with RWJBarnabus Health.

Andrew Schorr:  

Andy, let’s just start with you. So, news here that you wanna help patients and family members understand, and then we’re gonna get in to how you make decisions, how patients and family members make decisions. But, first of all, is there some news?

Dr. Brody:            

There is, and I would say there are multiple little updates, maybe no massive breakthroughs—at least, in the Hodgkin lymphoma.

There’re some data being presented on early-stage disease, and there’s often a discussion in early-stage disease where it’s only in a few places—do I give chemotherapy by itself? Do I add radiation or not? So, there’s some data presented there.

And then, in advanced-stage, I wouldn’t say we’re in a vacuum, but we’re in a place now of—there was a recent FDA approval for brentuximab vedotin (Adcetris) into the front lines, so I think we’re figuring out how and who that should be used for, number one, and number two, what are next steps. And then, for relapse refractory, it, of course, is novel agents. What are new drugs, targeted agents—including CAR-T cells—that we can talk about?

Andrew Schorr:  

Okay. So, Joshua, what’s your take on the news? Is it promising?

Dr. Brody:            

I think it’s extremely promising. As Andy says, we have little updates here, further updates from progress we’ve seen in the past year, most obviously this huge, I would say, breakthrough, which is that we can bring this targeted therapy brentuximab vedotin and antibody/drug conjugate into the front line of therapy.

And, that trial was the largest trial ever done in patients with Hodgkin’s lymphoma, more than 1,300 patients, and I would say a remarkable result, where they showed real benefit in the front-line setting using a combination of chemotherapy and what we call immunotherapy—antibody/drug conjugate. People overall are five percent less likely to progress or occur, but somehow, in the North American subgroup of people, it was much bigger than five percent. It was 11 percent benefit. So, that’s a real difference, and something that is, as Andy says, percolating through clinical practice. For some of us, it’s been practice-changing right away.

Andrew Schorr:  

So, tell us the symptoms that come on for people. Some of this may be brand-new. Somebody’s had weird symptoms, they said, “We think it’s Hodgkin lymphoma.” How does it present itself, Andy?

Dr. Evans:             

In different ways, but I would say the most common way, interestingly, is painless lymph node growth, or lymphadenopathy is a term we use.

And, it can be somewhat subtle, and even take weeks to months to progress, often in the neck, but it can be in other areas, and that’s probably one of the more common ways. Sometimes, there can be more systemic systems. There’s a term we use in lymphoma called “B symptoms,” which can indicate—drenching night sweats, unexpected weight loss, and high fevers. Not as common to see, but that’s also a way. There’s maybe some odd symptoms we see sometimes—weird itching in the absence of a rash that can happen as well.

Andrew Schorr:  

So, Joshua, it sounds like for the patient who’s having these symptoms, this less common disease—Hodgkin lymphoma—is not what somebody would go to right away and say, “That’s what it is.”

Dr. Brody:            

It really isn’t, and it’s so common—more the rule than the exception—that someone will have a lump in the neck, and they’ll see their primary care doctor.

And, the most common causes of lumps could be things like sore throats, where we get swollen lymph nodes as the result of a sore throat, and they’ll say, “Oh, did you have a little bit of a sore throat?” and the patient will say, “Well, yeah, a little bit,” and they’ll sometimes just treat them for strep throat or something. And then, patients are very surprised a month later when it doesn’t get better, and they eventually get a biopsy and show that this was Hodgkin.

They really shouldn’t be that surprised. That is more common that it happens that way because, again, Hodgkin lymphoma is rare compared to common things. What I think is a huge source of anxiety for patients and their families when that’s happened is, “Oh, we’ve lost time by virtue of this diagnosis not being made right away.” The truth is by the time we catch those, a few weeks here or there, the treatments are still extremely effective, so it really shouldn’t be such a source of anxiety for patients and their families.

Andrew Schorr:  

So, Esther, we have a daughter—25—and that’s one of the age groups right in it, and then, your parents are older –

Esther Schorr:     

Right. So, our understanding of Hodgkin lymphoma—you’ve got a sort of bifurcated group.

Dr. Brody:            

Yes, it is that type of camel, not the dromedary, but the other type of camel. It starts with a “B.”

Esther Schorr:     

No, no, the other one that has two places to store water.

Andrew Schorr:  

What are the age groups where this is, and do we know why?

Dr. Evans:             

That’s a good question. No, I don’t think we do. There are some theories, of course, but yeah, the term we use is “bimodal.” So, you see two peaks, I guess you could say, like a camel’s hump. The first is in your mid-20s to early-30s, and then it doesn’t go away, but becomes less common, and then it’s really in the 70s. Some people used to say 60s, but really 70s and early 80s that you see a second peak. Relatively speaking, it’s the same, but of course, absolute numbers—there’s more 25-year-olds than 75-year-olds. With that said, but probably 20-25 percent in the population of Hodgkin lymphoma are in that older age group.

Esther Schorr:     

Are the symptoms different in those two groups, or do they present the same way?

Dr. Evans:             

More similar than not. The only maybe difference in the older patients is they’re more likely to have advanced-stage disease, so it’s more two thirds of those patients will have—for older patients, advanced-stage. Younger patients, it’s more 50-50, early-stage advanced, maybe even a bit more early-stage, meaning just on one side of the diaphragm. Often, it’s above the diaphragm, just as Josh said, maybe in the neck, a couple areas there.

Andrew Schorr:  

But traditionally, you’ve done transplant and pretty aggressive therapy if people could withstand it, right?

Dr. Evans:             

Well, only for relapsed disease, not front-line. There have been studies looking at that. Before we had novel agents and maybe before Josh and my time, they thought more was better, so they would try to do transplants, and it was trying the best they can, but not for newly diagnosed. Only if it’s come back.

Andrew Schorr:  

Newly diagnosed, then, has been traditionally pretty aggressive chemotherapy, right?

Dr. Brody:            

So, we have—actually, as Andy says, really, a spectrum of aggressiveness. The tried and true chemotherapy over these past 40 years has been an intermediate aggressive chemotherapy we call ABVD, but there have been a lot of trials, more aggressive approaches, more so in Europe than America, a very aggressive approach called BEACOPP or escalated BEACOPP.

That chemotherapy is as tough as an autologous transplant, I would say, and ultimately, ABVD has still been the standard in America and most places in the world, and the question now is can we get a little bit away from the chemotherapy to try to integrate some of these targeted immune therapies into the front-line?

Esther Schorr:     

So, what are those new ones?

Dr. Evans:             

That’s the brentuximab vedotin.

Dr. Brody:            

So, in this big study, the brentuximab vedotin antibody/drug conjugate was the big event. It’s not a new therapy for Hodgkin—it’s seven years of FDA approval for later lines of therapy—but bringing it into the front-line—this is always the way that we discover and implement new drugs. We discover them in later lines of therapy for patients for whom standard things haven’t worked, and then, if they’re very promising, as brentuximab has been, we try to move it from third-line to second-line and first-line therapy.

Andrew Schorr:  

Okay, but my understanding is with this sort of lymphoma, treatment can be curative.

Dr. Brody:            

Absolutely.

Dr. Evans:             

The high majority of patients—so, that early stage, stage I or II, more than 90 percent of patients will be cured, meaning go away, not come back.

Esther Schorr:     

Both groups?

Dr. Evans:             

No—well, I would say early-stage is less common in the older patients, but probably both groups. And then, for advanced-stage, it still is high. It’s not as high as 90 percent, maybe 75 to 80 percent are cured, and that’s where there is some drop-off in the older patient, where historically, it had been quite low—actually 30 to 40 percentage points worse—and that had been a matter of debate. Why is that? Certainly, are you older, is it tolerability? Particularly, the bleomycin can be toxic to older patients in the lungs. But, we also think it might be a different biology—the older patients.

So, there are a few different subtypes of Hodgkin lymphoma. They tend to be a little different—something called mixed cellularity—you tend to see a virus inside the tumor called Epstein-Barr virus. So, it could be a little bit of both of why older patients historically had done not just a little worse, but actually a lot worse, so we think that’s changing too.

Esther Schorr:     

Interesting.

Andrew Schorr:  

You mentioned—so, I had never really thought about—you get a flu shot, and they talk about if you have a risk of Epstein-Barr—I don’t even fully understand it—but, did these younger people—and even older people—was there anything that happened to them that caused the Hodgkin lymphoma?

Dr. Brody:            

So far, I would say either no or nothing we’ve yet discovered. The Epstein-Barr virus has some association, but it’s sort of a loose association. We have other lymphomas where there’s a very clear association of that virus actually pushing that lymphoma forward, some of the rarer ones—MKT lymphoma, PTLD, some rare lymphomas. In Hodgkin, there’s some association, but it’s not as strong, and it doesn’t really seem that we could attack the virus to get rid of the lymphoma cells, or not as much.

Andrew Schorr:  

So, we don’t know whether somebody at college was exposed to something, or anything like that.

Dr. Brody:            

As best we can say, epidemiological studies have not been able to clearly show—so, we get Hodgkin lymphoma in poor people, rich people, boys, girls, old people, young people, as we’ve discussed, and there’s not a clear exposure factor we could associate with Hodgkin’s.

Andrew Schorr:  

Any racial differences?

Dr. Brody:            

Not significant ones, and not significant ones associated with other incidents or outcomes, ultimately. We do see this in all races.

Dr. Evans              

But, it’s important research, and it’s so hard to go back and do this epidemiologic research because we haven’t kept records of all your exposures, et cetera. There are some really good groups doing this in the world—the epidemiologic research—but we haven’t put the puzzle together yet.

Andrew Schorr:  

So, you used this word “cure,” which is great for a lot of people, but what if the first time around, you haven’t cured it. Does that take away all hope for people? What can you do when they’ve relapsed, or what you call “refractory” to the earlier treatments?

Dr. Brody:            

So, we’re very lucky that we do still have a chance for curing those patients—a reasonable chance. I’ll just say historically over the past few decades, the standard approach has been those patients get more chemotherapy—a different type of chemotherapy, sometimes—called “salvage chemotherapy,” usually what we call “platinum-type chemotherapies,” and those are a bit tougher than the front-line chemotherapy, and even if that chemotherapy is somewhat successfully, then we push ahead, and that’s that role of autologous stem-cell transplant.

All of those things together—we still think we can cure more than half of those people that relapse or don’t respond well to the first-line therapy. Those denominators are a little bit confusing because maybe not all patients get to all of those therapies. I will mention because we’re here at the ASH 2018 meeting—we’ve started to see more elegant ways of trying to take care of relapsed refractory disease.

One approach that’s been advanced over the last couple years is trying to get that targeted therapy into this second line of treatment, trying to use instead of the platinum chemotherapy, just that targeted antibody/drug conjugate, and there’s been some good results with that—a couple of groups at Sloan-Kettering, a couple of groups at City of Hope in California. And then, here at the ASH conference, we saw perhaps an even more elegant approach trying to combine that antibody/drug conjugate brentuximab vedotin with another great therapy we haven’t talked much about yet, another immunotherapy called an anti-PD1 antibody.

It really mobilizes the patient’s immune system to kill their own tumor cells, and a combination of those two has already been pretty effective for what we call third-line or fourth-line therapy, but a group has been trying to bring that into the second-line therapy to maybe be able to avoid some of that chemotherapy for the relapsed and refractory patients.

Esther Schorr:     

So, would that be a maintenance therapy at that point?

Dr. Brody:            

So, there are different approaches to it, but this group has mostly tried to use that at what we call “bridge to autologous stem cell transplant.” If the patients respond well and if they go into a partial or complete remission, they can go on to autologous stem cell transplant from there so that you’re able avoid some chemotherapy and get a very different way of killing those lymphomas.

Andrew Schorr:  

So, we’re talking about the immune system. How can we activate your immune system to target the cancer we missed the first time? So, Andy, in other hematologic malignancies, we’ve been talking about CAR T cell therapy—chimeric antigen receptor T cell therapy—taking your T cells, putting them in the lab, making them real strong, Hamburger Helper, attaching a virus to target the…

Dr. Evans              

…I like to say more Legos to get—it sounds a little more sophisticated compared to Hamburger Helper.

Esther Schorr:     

It’s a little cleaner.

Dr. Evans              

I am a little hungry right now.

Andrew Schorr:  

For the people who didn’t—where the initial therapy that could be curative didn’t work out for them, is there testing going on in CAR Ts for Hodgkin, and could that offer some way to activate their immune system to fight the cancer?

Dr. Evans              

The quick answer is yes, it has been. In fact, there was a presentation literally an hour ago that was just presented at the conference center looking at—so, it’s a different target. What’s been put forward so far FDA-approved are the CD19, which are on B cells, and so, that—Hodgkin lymphoma is a B cell lymphoma, but it’s an interesting thing of—and, by the way, we called this Hodgkin disease for over 150 years because we didn’t know until the 1990s it came from a B lymphocyte. We thought it could have been a virus or infection.

And, it’s interesting—it’s a B cell, but it almost intentionally down-regulates a lot of its B cell markers, so you don’t see it. It is a B cell marker, but what it does express is CD30. So, that is an antigen that’s typically on T cells –

Andrew Schorr:  

And monoclonal antibodies.

Dr. Evans              

Well, that brentuximab vedotin that Dr. Brody alluded to earlier is an anti-ADC to CD30. Okay, so, that’s good for an antibody/drug conjugate, but for CAR T, it’s actually a little bit more complex because that CD30 that I just mentioned is on normal T cells, and so, there’s some interesting aspects that I think can be navigated of if you’re putting an antibody on that T cell and reinjecting it, the issues you’re concerned about—obviously, you’d hope it all goes to the Hodgkin’s, but there’s a chance it could go after itself. It’s called fratricide. You don’t want the CAR T to go after itself, and certainly, you don’t want the CAR T to go after normal cells and get T cell aplasia.

So, those have been some theoretical concerns. I would say it’s a little farther behind—the B cell methodology—but it’s definitely there, and I would say it’s early, but promising.

Esther Schorr:     

So, these are not supposed to be a suicide mission.

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Page last updated on December 10, 2018