Targeting CD19 in Diffuse Large B-Cell Lymphoma - Episode 1

Current Treatment Approach to Relapsed/Refractory DLBCL

Targeted Oncology

John Pagel, MD, PhD: Hello and thank you for joining this Targeted Oncology® presentation titled, “Targeting CD19 in Diffuse Large B-Cell Lymphoma.”

Patients with transplantation-ineligible relapsed and refractory diffuse large B-cell lymphoma fare poorly and have limited treatment options. In today’s Precision Medicine in Oncology discussion, we will talk about the role of CD19 in this setting and how targeting this pan B-cell marker has led to new opportunities for treatment.

I’m Dr Ian Flinn. I’m the director of the Lymphoma Research Program at the Sarah Cannon Research Institute in Nashville, Tennessee.

Joining me today is Dr John Pagel, chief of the Hematologic Malignancies Program at the Swedish Cancer Institute in Seattle, Washington.

Thank you so much for joining us, and let’s begin.

So, John, we know there’s been tremendous advances in the treatment of large-cell lymphoma over the last 10 to 15 years. More recently, we’ve seen the introduction of CAR T [chimeric antigen receptor T] cells. Let’s talk about large-cell lymphoma in general to begin with. How common of a disease is this, and what percentage of patients ultimately relapse from their therapy?

Hi Ian, it’s great to be with you. Of course, we’re doing this on opposite sides of the country but certainly can communicate quite well about this topic, and it’s an honor to be with you guys today.

You’re right, large-cell lymphoma has really been our success story in non-Hodgkin lymphoma. You know, 20 years or so ago, the big deal of course, was rituximab and its introduction to the CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone]-based chemotherapy backbone. The addition of rituximab certainly provided major benefits for overall patient survival. And because of that, we’ve been able to be very successful in curing probably 50% to 60% of patients, or more, in the upfront setting with standard R-CHOP [rituximab cyclophosphamide, doxorubicin, vincristine, and prednisone]chemoimmunotherapy.

There’s been a big lag and a lull between the introduction of rituximab and major improvements in the outcomes for patients with large-cell lymphoma, until just more recently with a lot of the things that we’re going to discuss in this program.

It’s important, of course, to recognize that we want to cure as many people as we possibly can—this is a curative disease where we approach it with curative intent. We, however, have to recognize that maybe about a third of patients, 30% to 40% of patients, will relapse from their lymphoma, and many of those people might not be eligible for a stem cell transplant, which has traditionally been our standard of care in the relapse setting.

So, I would say a lot of people still relapse. They still need to do better not only in the front-line setting, but I think we need to do better in multiple relapse settings as well with large-cell lymphoma to improve outcomes for these patients.

Ian Flinn, MD: Yeah, and I think you’ve brought up a number of good points. Thankfully, a lot of people are cured of their disease up front. But many people are not.

And in that setting, what do you do? We try to get patients to transplant, but unfortunately those patients that relapse within their first year (which is the majority of patients) don’t do well and their outcomes are poor.

We’ll talk a little bit about CAR T cells in a moment. But first, other options. We’ve had options to work with the drug polatuzumab, both by research studies and now that it’s commercially available. And that’s definitely an improvement in our armamentarium. The studies show that maybe 60% or more patients will get a response, but unfortunately these remissions, progression-free survivals, they’re not as good as we’d want them to be—in the neighborhood of 6 months. And so we have a lot of work to do there. What is your approach in patients who relapsed and perhaps are transplant ineligible?

John Pagel, MD, PhD: You’re right. I think polatuzumab has been an advance. It’s certainly something that we have in the tool kit now that we can use for patients when we have very limited options. Fortunately, it’s not our only option at this point. I do like the polatuzumab, as you do, in the right situation. It’s of course approved with bendamustine in patients who have relapsed, but frankly I think the activity of the drug is just as good without the bendamustine in these types of patients who are often chemotherapy refractory.

The thing that I always have to remember with polatuzumab, and I’m sure you do too, is that it does have some toxicity. I do worry about the neurotoxicity occasionally with that agent and often look to that as a bridge to transplant for many patients. Because of that short duration of remission or short progression-free survival that you just alluded to, I’m looking for other things in the patients who are not eligible for transplant. And 1 of the things that I think we’re finding very exciting in those patients, that it can be a significant benefit for them, are Revlimid or lenalidomide-based regimens.

So even though not approved in large-cell lymphoma, there are significant patients who are not eligible for transplant, in my opinion, who can benefit from R-squared [Rituxan plus Revlimid]. And, again, it’s not approved in that setting but it’s something we’re doing in the right setting because of its tolerability and that people can do well. In particular, as you know, those are the ABC [activated B-cell]subtypes in large number with relapsed large-cell lymphoma,

We’re obviously, and I’m sure you are too, looking for new agents, and I think that’s why the anti-CD19 agents—the bispecific and certainly CAR T cells—are really game changers for these patients who are ineligible for transplant, or even for those who were unsuccessful with an autologous transplant.

Ian Flinn, MD: Yeah, we are looking for new agents in large-cell lymphoma for sure. And you brought up 1 important dividing point, which is whether someone’s transplant eligible or ineligible, and what makes them eligible. At least at our center, we no longer have a chronological age for which we stop doing transplants. So, patients well into their 70s will sometimes be eligible for an autologous stem-cell transplant as long as their physiological age is good. Meaning they have good cardiac function, good lung function, good renal function, and good performance status.

But of course, to be eligible for a transplant, you have to have sensitive disease, and I think that’s really one of the sticking points in getting patients to transplant is that they’re insensitive.

Transcript edited for clarity.