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Late Stage Diffuse Large B-Cell Lymphoma Treatment Options

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Published on July 15, 2020

Late Stage Diffuse Large B-Cell Lymphoma Treatment Options

New treatments offer lots of options for late-stage diffuse large B cell lymphoma patients. Dr. Erlene Seymour from Karmanos Cancer Institute joins Patient Power co-founder, Andrew Schorr to explain diagnosing advanced DLBCL, the standard therapy R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone) and the new medications that are being used in combination with R-CHOP.

Dr. Seymour explains how CAR-T cell therapy, Bi-specific antibody therapies and new oral medications are all being used in the treatment of late stage DLBCL.

While several oral agents, including the recently approved selinexor, are being used for treatment by themselves, ongoing research on how oral agents work with other treatments shows great promise for advanced-stage DLBCL patients.

Disclaimer: This program is sponsored by Karyopharm Therapeutics. This organization has no editorial control, and Patient Power is solely responsible for program content.

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Transcript | Late Stage Diffuse Large B-Cell Lymphoma Treatment Options

Andrew Schorr:
Hello, and welcome to Patient Power. I'm Andrew Schorr and joining me from the Karmanos Cancer Institute in Detroit is Dr. Erlene Seymour who's a lymphoma specialist. Welcome to Patient Power.

Dr. Seymour:
Thanks for having me.

Andrew Schorr:
Dr. Seymour, let's talk about diffuse large B cell lymphoma. My understanding is it's the most common of the non-Hodgkin lymphomas and it can be aggressive. Let's talk specifically about what you do when it's later stage.

Dr. Seymour:
When it's later stage, often our patients are having symptoms. Later stage means you've got lymph nodes in your chest area, also in your abdomen and oftentimes because it is a blood cancer and this it's not unusual for lymphoma to do, we'll see it involving organs outside of the lymph nodes, outside of the spleen, which is typical of your lymph system. For later-stage lymphomas, the nice thing about lymphomas, particularly diffuse large B-cell lymphoma, which you said is the most common, even if you are advanced stage lymphoma, you have potential for a curative response. The cure rate when you're very advanced stage is not as good as a lower stage diffuse large B-cell lymphoma. However, it's still there. And that's to be said. It's not something that every stage four cancer has. What I tell patients is when they have advanced stage lymphoma, that their cure rate can be as low as 50%. However, we're still talking about potential curative options.

Andrew Schorr:
The word cure is a great, great one. Now, first of all, when you suspect that somebody's at a later stage, how have you done that? Have you done some, besides the symptoms, have you done some sort of scan?

Dr. Seymour:
Typically, at the beginning, we'll certainly get something called a PET scan. It's nicer to have it with a PET along with a CT scan to get exact detail. Oftentimes depending on the situation, say, it's somebody in the hospital and they're very symptomatic and they need treatment right away, sometimes we can only get the CAT scan, but typically you will want a PET scan or a CAT scan that gets from your head down to your thighs. And that will give us a lot of information as to which lymph nodes are bigger and the PET scan, in particular, tells us which sites are active with your cancer.

Andrew Schorr:
Okay, here we are in the middle of 2020, you have very recently a new approval for a medicine for, I believe this situation and you were one of the investigators. Tell us, what's your range of treatments now for people with later stage diffuse large B-cell lymphoma?

Dr. Seymour:
Well, so that's a hefty question because there's a lot of options. For late, let's say you haven't been treated before you come to me with advanced stage lymphomas. In that situation you haven't been treated before, the standard of care is still chemotherapy along with something called rituximab (Rituxan). Okay, so I'm just going to preface that as calling it chemo-immunotherapy.

Andrew Schorr:
R-CHOP, I think.

Dr. Seymour:
R-CHOP. But in some certain situations, we may think of something called dose-adjusted R-EPOCH for more advanced diffuse large B-cell lymphomas. For instance, if they have mutations that cause us to call it a double hit lymphoma. In that situation, sometimes we will think about doing dose-adjusted R-EPOCH, still chemotherapy, along with rituximab, however. It's kind of in the same category, but a different regimen. That's what we would do for frontline therapy as standard. There are lots of trials out there looking at novel agents in combination with R-CHOP, in combination with dose-adjusted R-EPOCH, to see if we can improve upon that.

Now that gets tricky because so far it's really hard to beat R-CHOP when do we put in a novel therapy along with it. However, there's a lot of novel therapies out there that are now approved for relapsed refractory diffuse large B-cell lymphoma. Let me tell you about the more exciting ones because there's a whole slew of them. Say, you're the unlucky 50% that relapse the second time around. It's been a couple years since you're relapsed. Often we will think about chemo-immunotherapy again, actually. Often it'll be something called RICE or something called RGDP, whichever chemotherapy we can think of at the time that you can handle to get you to an auto-transplant. And essentially an autologous transplant is a transplant taking your own cells. And then you come in, you get harder chemotherapy, we give you back your cells and we're trying to again, give you actually a chance of cure at that point.

However, the percentage of cure is much lower, particularly for advanced-stage lymphomas. What can we do with, this is what we call salvage therapy. What's really exciting as far as the clinical studies out there is CAR T-cell therapy. We're actually having trials, comparing CAR T-cell therapy with autologous transplants. Seeing which is better. And CAR T-cell therapy takes your own T-cells, so your normal T-cells, re-engineers them to specifically target your diffuse large B-cell lymphoma cells and we infuse that back, right back to you. CAR T-cells are very exciting therapy, particularly we have to answer whether that's better in second-line compared to transplant. We do not know the answer to that yet, but we certainly will in the next couple years.

Then we think about what if you relapse past that? Now we have a lot of patients who relapse past transplant and we even have some patients now that relapse past CAR T-cell therapy. We're now in this age where we're seeing relapse after CAR T. There's a lot of agents at that point that are still exciting to us that we are trying now that have been approved or have been, are still being studied. Of these classes of drugs that I'm probably most excited about, there are something called bi-specific antibodies. They are antibodies that target your cancer cells but also target your normal T-cells to try to enhance that attack against your cancer cells. There are something called antibody-drug conjugates. Now, when I'm talking about all of these, these are all infusions - so that's important. You still have to come to clinic. You still have to get an infusion. It happens every couple weeks when you get the infusions. And often at the beginning, you might have to be inpatient, particularly for the bi-specific antibodies.

The other class of drug that is exciting here is antibody drug conjugates. Those are antibodies that target your cancer drugs, your diffuse large B-cells, but also throw in a toxin. There are several out there right now. One is called polatuzumab (Polivy) that was approved to be given with chemotherapy. There's also brentuximab (Adcetris) for the small amount of diffuse large B-cell lymphomas that can express CD30.

And then there are oral agents. There's actually multiple oral agents that we can still use. It is not uncommon for me to treat someone with diffuse large B-cell lymphoma and we have seen three or four therapies on them. And they are still actually getting therapies that may work because often these, all of these agents are still in clinical studies and we're trying to find the right combinations. And we're trying to find something better than chemo-immunotherapy. We're trying to find something better than chemotherapy with rituximab, particularly if you failed that in the past.

Of the oral agents, there are pills, so some of the pills are lenalidomide (Revlimid), ibrutnib and the one that you said was recently approved is selinexor (Xpovio). What's interesting about the oral agents is we have some hint that they work by themselves, but we would like to know if they work better in combination with all these other agents that I just spoke about. And I think that's where that's going to be exciting, because like I said, it would be nice to find something that could be better than chemo-immunotherapy, particularly if you've already failed it.

Andrew Schorr:
Okay. Let me ask you, you mentioned selinexor, so that's a whole new class of medicine, right?

Dr. Seymour:
Yes.

Andrew Schorr:
I know it was approved very recently. So, you have this range of treatments. It sounds like you have more options than ever before to give people hope.

Dr. Seymour:
Absolutely. And that's why clinical trials for diffuse large B-cell are very exciting right now.

Andrew Schorr:
Okay. There's no free lunch in cancer therapy.

Dr. Seymour:
Free lunch.

Andrew Schorr:
These are powerful medicines. And so there are side effects. How do you manage side effects?

Dr. Seymour:
All of the drugs that I mentioned, the side effects are actually quite unique to every drug. Say chemo-immunotherapy, I think they're all pretty similar. You have an increased risk of infection that often causes hospitalizations. You can have what we call peripheral neuropathy or numbness and tingling in your hands and feet. And the other thing with most chemo-immunotherapies is you lose your hair, albeit temporary, but you lose your hair. The side effects of those are pretty well managed with we give growth factor support so that means we give injections to help your white blood cells stay up. We give you nausea medications, honestly, a big change in the last two decades is having good antiemetics. And so we use antiemetics with all of these regimens. And depending on, and it's certainly unique to each regimen, which antiemetics work best. We also make sure that we're checking blood counts to make sure that there no transfusions are needed, but that honestly rarely occurs except for RICE and autotransplant. Other side effects… I think those are the most common.

Andrew Schorr:
I know that this drug selinexor a new class is a pretty powerful drug. You mention antiemetics or anti-nausea drugs that really comes into play there, but you do have antiemetics to help.

Dr. Seymour:
Yes. We have oral antiemetics that help. There are injectable antiemetics and there are oral antiemetics. And at least in my experience with my clinical trials, we've stuck to oral antiemetics. And it works quite well actually with that drug. I often do have to use two different types to really help patients because in prior trials, we did see a lot of nausea vomiting at the very beginning when this was dosed higher. And now that now we know how to give it at lower doses with proper antiemetics and it's better tolerated.

Andrew Schorr:
Alright. Given this range of treatments that you have, it still seems like there's a great deal of hope for people, but this is the art of medicine, as you figure out dosages, side effect management, and which patient gets which treatment when. I think it's a hopeful time for people even where they've had later stage or relapsed diffuse large B-cell lymphoma.

Dr. Seymour:
Oh, absolutely. Absolutely it is.

Andrew Schorr:
Let's talk for a minute about clinical trials. So you have some newly approved drugs over this last few months. You have tweaking of some other therapies you've had for a while and then you have clinical trials. You're a researcher, so what are you excited about related to clinical trials? And why should people talk to you about it?

Dr. Seymour:
There's a lot of novel agents out there and we've looked at them in monotherapy and I think it's going to be really interesting to see them in combination therapy. Now that we actually have a lot of novel therapies, they have unique toxicity profiles, but I have been an investigator on actually several of these combination regimens to see if we can do better than standard of care. Especially in a patient who is going to relapse through chemo-immunotherapy and through CAR T therapy, it's important.

Andrew Schorr:
I do want to ask you about CAR T therapy. It is approved for diffuse large B-cell lymphoma. What do we know now about how long it lasts?

Dr. Seymour:
I think it varies and it also depends on the patient, how aggressive the patient is when they go into CAR T therapy. At least in my experience, if it's somebody who is refractory and is going in with a very aggressive disease, it's hard to contain. But that being said, I still see patients with advanced-stage diffuse large B-cell still get really good responses with CAR T therapy. I would say our experience is as far as the durable remission, I think it occurs about 40% of the time. We are certainly seeing people relapse now with CAR T therapy. When it works, it works and that's great, but when it doesn't work, then we need some other options. And I think the nice thing about this time as we do have other options and now the trials are opening to those patients who are CAR T relapsers and we're seeing some efficacy with these agents.

Andrew Schorr:
Alright. Well, to pull it all together though, diffuse large B-cell lymphoma is often cured. The cure rate goes down if people have a more aggressive situation or a relapse, hope is not gone. And so it sounds like you have more to offer people than ever before.

Dr. Seymour:
Yes, that's absolutely true.

Andrew Schorr:
Okay. Well, thank you for the work you're doing with patients. I'm so happy there are new approved additions, and more in clinical trials and you're putting these puzzles together of combination therapies and then you have supportive care to help people with the side effects. Thank you so much for being with us, Dr. Erlene Seymour. We really appreciate it.

Dr. Seymour:
Thank you.

Andrew Schorr:
I'm Andrew Schorr. Remember, knowledge can be the best medicine of all.

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