Emerging Therapies for R/R DLBCL


John P. Leonard, MD: I want to move towards, in our last few minutes, talking about other agents. We've talked about a couple that are either approved or farther along in the regulatory review process. I remain struck by the number of agents that continue to be studied. You might think that we've reached our limit, so to speak, in immunotherapies and antibody-based therapies, but there a number of bispecific antibodies and there are versions of bispecific antibodies where different companies have engineered their own version of a bispecific or a new type of antibody. We have antibody drug conjugates. We have the bispecific T-cell engager [BiTE], blinatumomab, approved in certain settings. What do you think about—before we get to other categories of drugs that you're excited about—these novel immunotherapies, for lack of a better term?

I'll ask Matt to go first, and then Kami and Nathan, and share your thoughts on where these fit. Some of them have data, both the antibody-drug conjugates and the bispecifics, that are approaching or even better than some of the things we talked about today. So Matt, your thoughts.

Matthew Lunning, DO: Some of the bispecifics, like glofitamab, which has 2 different binding domains; CD20 that then engage CD3. You have—it's always fun trying to learn the new names—epcoritamab, which is a subcutaneous injection going after the same space. It's going to be generating data but not a lot of the data will follow CAR T. We’re going to get response rates and PFS, but they aren't going to be in the population where you enter the playing field.

It's great to have the data because if you don't have data there, you're not going to want to go into those populations. I'm excited about seeing those drugs get a longer follow-up. We've got the overall response rates and CR rates, but we need durability.

John P. Leonard, MD:Kami, your thoughts?

Kami Maddocks, MD: There's still some good data out there. There are 3 CD19 ADCs that have been developed, all showing pretty similar responses, however 2 are not going to be further developed due to toxicity. The third one had good responses that don't last long and is probably going to have to be in combination—kind of like some of the other agents we talked about today—to really get good remissions. I think the bispecifics are interesting. A few of those have been looked at in the post-CAR T setting and have activity there, which is probably one of the highest unmet needs of those patients who are post CAR T.

Matthew Lunning, DO: Mosunetuzumab had a couple of post-CAR T patients on it, if I remember the data correctly.

John P. Leonard, MD:From the ASH 2019 plenary.

Kami Maddocks, MD: Yes, that one and then the Regeneron Pharmaceuticals one just recently put out data with some responses post CAR T. We have potential therapies, like selinexor, to offer those patients.

Matthew Lunning, DO: At least it shows that they're listening to us because a lot of trials have been trying to write off patients by not allowing prior exposure to CD19 CARs. Why are you doing that? That's exactly who we should be studying. Yes, create an expansion cohort for all you want and analyze the data differently, but we need to understand that population.

John P. Leonard, MD:Nathan, your thoughts on some of these new drugs?

Nathan H. Fowler, MD: I will echo what everyone said already. When we were looking at the BiTE molecules a couple of years ago, there was some sense that they would maybe displace CAR Ts. But a lot of the data that were seeing now is immature. I don't think that the durable CR rate appears to be at the same level that we're seeing with CAR T-cells, at least in large cell lymphoma. So I don't see these replacing CAR Ts, but I agree with Kami and Matt that they will probably follow CAR T as a salvage for these patients.

The other thing I thought at this most recent ASCO, there was a nice abstract on AlloCAR T and it would be very interesting to develop an off-the-shelf strategy for CAR T where we you would have something that's sitting in your blood bank and able to be given to patients when they relapse. Those studies are still very small, but that would be something we should consider more.

John P. Leonard, MD:Matt, you've talked about the access and applicability of CAR T. It strikes me that there's a large percentage of people who could benefit from CAR T that are not getting them. It also strikes me that having new agents around is going to make that number of patients getting CAR T even smaller because there will be alternatives. Whether or not they're appropriate, it's good for patients to have alternatives.

The fact is people will be more inclined to say “You got to go get CAR T.” And now the discussion will be, “You should get CAR T but you could get this or that.” How do you think that's going to change the big picture?

Matthew Lunning, DO: I still have a lot of hair to pull out in my career, but I think it just comes back to being a resource to have those discussions about who in this population is appropriate to go to CAR T cell and who isn't. It's great that we're getting all of these new classes, more drugs to have the discussions about. It's a chess match against large cell lymphoma and knowing what piece to play next; You may be moving 1 piece to make a move 3 times down the road and that may be CAR-T-cell because that's what the data shows.

We have to continue to encourage that if you're doing a CAR T-cell study, you should be able to get a CD19 BiTE or you should be able to get a CD19 antibody for the CAR T cell so that we know and can inform the patients about this. We want to not exclude the patients from the studies so that they can't get a CAR T-cell or the next generation CAR T-cell because that may be the patient population that does derive benefit.

John P. Leonard, MD:So Kami, you at Ohio State University Medical Center clearly have lots of access to CAR T, yet you’ve been participating in a variety of different trials, including some of the agents we've talked about today, which in some ways tells me that you see excitement and promise in some of the things that are not CAR Ts that we've talked about, that they're fulfilling or potentially filling a need for your patience. Why do you think that is, from the standpoint of just ease and toxicity?

I’m putting you on the spot here but I just want to see how people in practice should think about this. Clearly, going on a trial with tafasitamab offered something to those patients that was attractive. So how do you think about it because I think it's the same way people are going to have to think about it in practice.

Kami Maddocks, MD: When looking at your patient, you need to know what are they able to tolerate if something is very well-tolerated and they can get a good response from it. Regarding access, they have to come to us for the trial, but just in general, Ohio serves a big population. There's a lot of land here for a small amount of people so we serve a number of states. When you're looking at making recommendations for therapy, not everybody can have access to the big center; not everybody can wait to have their CAR T sent off, manufactured, and returned and not get therapy in between that time. Sometimes it's still an insurance issue or a financial issue; you have to have the coverage and pay what isn’t covered. You have to stay within a certain closeness to Ohio State for a certain amount of time after you leave the hospital. All those represent challenges for our population in this area.

Transcript Edited for Clarity

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