Tag Archive for: relapsed DLBCL

Which Emerging DLBCL Therapies Are Showing Promise?

Which Emerging DLBCL Therapies Are Showing Promise? from Patient Empowerment Network on Vimeo.

What’s next in diffuse large B-cell lymphoma (DLBCL) treatment? Dr. Justin Kline reviews developing research that could transform the future of DLBCL treatment.

Dr. Justin Kline is the Director of the Lymphoma Program at the University of Chicago Medicine. Learn more about Dr. Kline, here.

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What about emerging therapies, Dr. Kline? What approaches are showing promise?

Dr. Kline:       

Well, I think probably in DLBCL, the biggest breakthrough, I don’t even know that I can call it emerging at this point, because it’s on the market, so to speak.

But I think it’s important to talk about, again, is CAR T-cell therapy, and this is a type of immune therapy where a person’s own immune cells called T-cells are taken from his or her bloodstream. And then using a special type of a virus, those T-cells are manipulated or engineered, that sounds better, to express on their surface something called a chimeric antigen receptor, which is somewhere between an antibody and a normal T-cell receptor. But anyhow, this chimeric antigen receptor confers or allows the T-cell to recognize a protein that’s expressed on the surface of B-cells, cancerous or otherwise, called CD19. And when that chimeric antigen or CAR antigen, excuse me, that CAR receptor expressing T-cell sees a lymphoma cell, it engages it and kills it, a pretty clever idea which has been in the works for decades now.

But CAR T-cell therapy has now been approved for not only DLBCL but many other types of non-Hodgkin lymphoma. And I think in the past decade, far and away, that’s the biggest breakthrough. There are other types of immunotherapy, probably most notably a type called bispecific immunotherapy, which is a pretty clever type of immune therapy where these specially engineered antibodies that are capable of binding or sticking to not only a person’s T-cell, a T-cell that’s already in his or her body, and a B-cell, a lymphoma cell that’s right next to that T-cell, sort of holds them together, and the part that binds the T-cell actually activates it, triggers it to kill the B-cell. And so there are a number of companies that have those bispecific therapies that are in development. I suspect a couple will be approved by the FDA, I would guess, in 2022.

These bispecific immunotherapies have been very effective, again, in DLBCL that’s come back, relapsed or refractory, as well as in other lymphomas. They do have some side effects that are similar to what we see in folks with CAR T-cell therapy. I won’t belabor what those are, but they are also very effective. There’ve been a number of drugs that, either immunotherapies or other types of therapies, that target that same CD19 protein on diffuse large B-cell lymphoma cells that have recently been approved by the FDA, either alone or in combination. Targeted therapies are always exciting. Although as compared with other lymphomas, these targeted therapies, many of which are oral, which are pills, have not been particularly effective in relapsed DLBCL.

So, I think that among the most exciting therapies are those that take advantage of our own immune systems to recognize and kill the lymphoma cells.

An Expert Review of DLBCL Research and Treatment Advances

An Expert Review of DLBCL Research and Treatment Advances from Patient Empowerment Network on Vimeo.

What’s the latest in diffuse large B-cell lymphoma (DLBCL) treatment advances? Expert Dr. Robert Dean provides an update about emerging DLBCL research and explains recent treatment approvals for relapsed DLBCL patients.

Dr. Robert Dean is a hematologist/medical oncologist at Taussig Cancer Institute at the Cleveland Clinic. Learn more about Dr. Dean, here.

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Is there emerging DLBCL research that you feel patients should know about?

Dr. Dean:

I would say, “yes.” One of the things that has really been striking for me in the last few years alone in caring for patients with large B-cell lymphoma is how we’ve gone from a more surface-level understanding as we’ve been talking about what some of the differences are between different cases of large B-cell lymphoma to being able to get a better readout of why the lymphomas sometimes behave the way they do.

I want to be careful to make sure that patients who might be listening to this understand that we still don’t have a crystal ball. We can’t review their biopsy, look at their scans, and tell you, “I know that if you get R-CHOP you’re going to be cured.” Or if they’re a high-risk situation we can’t look into a crystal ball and tell them, “I know that R-CHOP won’t work for you, and you should do this tougher, more intensive treatment.”

We still see a lot of outcomes that we can’t necessarily predict from those other kinds of tools. They just give us a better sense of what the odds are for people as we’re at the start trying to make decisions about what to do. Another element that has really been striking has been the introduction of engineered T-cell immune therapy, which has provided an option for cure for some patients that otherwise we wouldn’t have had an option, and worked for about half the patients that go through it overall.

What’s coming down the road in clinical trials that are still ongoing is information that’ll help us decide if that approach to treatment should move to being second in line instead of a stem cell transplant for some patients, and they’re even doing studies looking at whether, for very high-risk patients, adding a CAR T-cell treatment onto the end of initial chemotherapy leaves them better off in the long run.

So, those are questions that will take some time to answer with ongoing studies, but I think are really exciting because they’re taking advantage of some of these newer treatment approaches that we know are helping some patients when their first attempts at treatment didn’t work and seeing if they might leave them better off if we use them earlier in the process.

There are other studies ongoing looking at seeing if we can improve upon the results that we get with treatments like R-CHOP as the first pass at treatment. Many such studies have been done and have not shown any benefit by adding this drug or that to the standard R-CHOP treatment, but there have been a few new drugs approved for treating people with large B-cell lymphoma after it’s relapsed in the last few years. For example, one called polatuzumab vedotin. Another combination of the drug lenalidomide and a new antibody-based drug called tafasitamab.

And then there’s another drug called loncastuximab. So, there’re studies going on with all of those looking at whether they offer more benefits to patients if we use them earlier in the game.