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Treatments for Relapsed Diffuse Large B-Cell Lymphoma

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Published on July 14, 2020

Diffuse large B-cell lymphoma patients can relapse when they develop a resistance to their medication. What treatment options are available when someone relapses? What new research is available regarding relapsed aggressive lymphomas? When is CAR T-cell therapy an option?

Dr. Jason Westin, from the University of Texas MD Anderson Cancer Center, discusses the advances in treating this type of non-Hodgkin lymphoma after a relapse, new FDA approved diffuse large B-cell drugs and new drugs in development.

Dr. Westin walks through several modalities used to treat relapsed DLBCL including CAR T, antibody drug conjugates, and targeted and combination therapies. Watch to hear an update on CAR T-cell therapy, which Dr. Westin describes as a “transformative technology” for relapsed diffuse large b-cell lymphoma patients, and ongoing research to improve patient response. 

This is Part 3 of a 4 part series, watch Part 1 Causes and Symptoms of Diffuse Large B-Cell Lymphoma, Part 2 Treating Diffuse Large B-Cell Lymphoma, and Part 4 DLBCL Treatment Research: Moving Beyond R-CHOP.

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Transcript | Treatments for Relapsed Diffuse Large B-Cell Lymphoma

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. We're talking about Non-Hodgkin's lymphoma and specifically diffuse large B-Cell lymphoma, which is an aggressive lymphoma. And with us is an expert in that Dr. Jason Westin from MD Anderson in Houston. Dr. Westin, first of all, you've got a long title. We want to make sure we get it right. What is your title there at MD Anderson?

Dr. Westin:

Sure. Hi Andrew. Thank you for having me today on Patient Power. I at MD Anderson am the Director of Lymphoma Clinical Research and the Section Chief for Aggressive Lymphomas.

Andrew Schorr:

Let's talk about in the relapse setting, if you will. So the first line of treatment chemo or R-CHOP didn't get rid of the cancer. So you have a discussion with patients based on their fitness, for example, on an autologous transplant. And that is cleaning up their own cells, their own immune system to try to reboot their immune system, but with their own cells, not cells from someone else.

Or what you mentioned, CAR T chimeric antigen receptor T-Cell therapy, where basically you make a drug with their T-Cells in the lab, and then you infuse it back to go after the cancer cells that were missed. So this may be changing. So first of all, CAR T, are you excited about that? It is approved for some lymphoma patients, so help us understand where that comes in.

Dr. Westin:

Yeah. CAR T is something that I am very excited about, and I think it is a transformative technology for our patients with relapsed diffuse large B-Cell lymphoma. There are some other cancers, some leukemias, multiple myeloma, other types of lymphomas where CAR T-Cells are also showing great potential.

So this is not only for diffuse large B-Cell lymphoma, but their results perhaps have been greatest so far in diffuse large B-Cell lymphoma patients. It is a wonderful advance for people that have had resistant lymphomas to several lines of treatment and the early clinical trials we've now been able to follow on some of our patients for up to or beyond three years and have seen a durable response.

And this is a onetime treatment. As you mentioned, we're taking somebodies immune cells, their T-Cells out of their body, sending them off to the lab to basically weaponize those cells. If we think of the immune cells in the body as the basic infantry of the soldiers that are doing their best, but not elite, that are not able to fight the cancer, these new cells are sent off to bootcamp.

They're basically now the Army Rangers or the Navy Seals or whatever elite fighting force you want to call them. And when they're reinfused into the same patient they were taken out of back home, these are now able to see the wolf in sheep's clothing and to attack and to overcome some of the resistance that may have occurred to previous treatments.

It's not a guarantee, but the response rates for CAR T-Cells in the earliest trials range between 50 to 80% of patients who achieved a great response and slightly less than 50% of people who received the CAR T-Cells in the first trials have remained in a very durable remission. Contrast that with other chemotherapies, for relapsed refractory patients in a third line or fourth line or beyond setting, that's off the charts in terms of what we'd seen previously.

So this is changing the world in terms of how patients with relapsed aggressive lymphomas can view their disease. We're hoping we can move this even earlier and have a greater chance to cure even more patients with this new amazing technology.

Andrew Schorr:

Dr. Westin. So beyond CAR T, there are other medicines that are in development, some even approved. So where does that fit in, for patients now?

Dr. Westin:

There have been several approved agents in the relapsed diffuse large B-Cell lymphomas space over the past year or so. The one that was approved in terms of chronological order longest ago is an antibody drug conjugate called polatuzumab (Polivy).

And this is basically an antibody like your body would make against an infection, but this antibody is made in the lab to target a protein that's on the outside of B-Cells, and usually cancer B-Cells like diffuse large B-Cell lymphoma express this protein called CD79b.

This antibody, however, has a neat trick. And then on the back end of it is a chemotherapy warhead. So it's basically like a heat seeking missile. It's introduced in the body and is able to target delivery of chemotherapy specifically to the tumor cells in a way that avoids some off target toxicities. So that drug polatuzumab has been approved for patients with relapsed diffuse large B-Cell lymphoma in combination with rituximab (Rituxan) and a chemotherapy called bendamustine (Bendeka).

Just recently, before we taped this episode, there was an approval of another drug called selinexor (Xpovio), which is an inhibitor of a protein that helps kick out proteins from the nucleus. It's kind of a very interesting mechanism that it blocks that kicking outs proteins from the nucleus and preferentially in cancer cells, they're sensitive to that. Keeping so-called tumor suppressor proteins in the nucleus, and that is a new option.

And there are others which are likely to be approved in the next couple of months. There's an antibody called tafasitamab (MOR208), lenalidomide (Revlimid). Tafasitamab combined with lenalidomide, which has shown incredible results. And although it's not yet FDA approved, it's very intriguing and potentially could be on the market by the end of this year.

I'm not the FDA. I don't know what they'll say, but I think that that one has a lot of people interested as a relapsed lymphoma drug. Now, your original question is how do you view these drugs and how would you potentially rank them or how would you view them versus CAR T-Cells? We don't know for sure yet, if any of these new agents has the long term potential that a CAR T-Cell therapy appears to have.

And so for most patients, what we would recommend, if you can get access to either one, if your doctor says, well, we could do this, or we could do that. I would recommend that being evaluated by a CAR T-Cell center or a CAR T-Cell expert should be done by every patient with relapsed diffuse large B-Cell lymphoma, because if it were my patient and we had access to either one, if the goal is to try and cure the disease, CAR T-Cells are more difficult, CAR T-Cells can be costly, they're quite logistically challenging, but they have the potential for that long term control or what I would call cure of the disease. I don't know if the other therapies do have that.

Andrew Schorr:

Okay. Taken together though, it sounds like for diffuse large B-Cell lymphoma patients, you have a range of treatments and you're involved in ongoing research that the story continues to improve for many people to give patients and their families the hope for a longer life, and maybe cure.

Dr. Westin:

And maybe cure, that's exactly right. So this is an aggressive cancer. And as we said before, those two words together are not something you ever want to see somebody like me sitting with the white coat across the exam room mentioning those terms, but this is a treatable cancer. And there's an incredible number of new advances that are both available today, as well as in the pipeline coming in the future.

The future is incredibly bright for treating patients with diffuse large B-Cell lymphoma. Patients who are treated with standard options and have not considered a clinical trial, or have not been referred for a CAR T-Cell, I would advise you to seek out a second opinion or to come visit somebody at an academic cancer center, if at all possible, because some of the new advances are really transformative and potentially can extend life or even get rid of the disease for good.

But if you don't talk to somebody who does lymphoma on a regular basis, or who's an expert in lymphoma, sometimes it's hard to keep up with all these advances and have your finger on the pulse of all these fast moving developments. So it's very important to seek that expert opinion if you're dealing with this disease.

Andrew Schorr:

A hopeful story, a positive story. Dr. Jason Westin from MD Anderson and a lymphoma specialist. Thank you for explaining this to us, and your work in moving research forward, so that the options that can help people continue to grow. Thanks for being with us.

Dr. Westin:

Thank you for having me, it's my pleasure.

Andrew Schorr:

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

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.

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