The Future of DLBCL Management


Ian Flinn, MD: Let’s talk about other drugs that are in development in large-cell lymphoma. Have you been using any of the other antibody-drug conjugates?

John Pagel, MD, PhD: You know, one that I’m excited about in development is from a small company known as Veloce Bio. It’s an antibody-drug conjugate that targets a whole different new class of antigens. It’s called ROR1[receptor tyrosine kinase-like orphan receptor 1]. It’s a target with a conjugate, the standard conjugate that was used in many conjugated antibodies now—MMAE [monomethyl auristatin E]. The same one that we see with brentuximab vedotin, which we use in the front-line [setting] for some patients with relapsed Hodgkin lymphoma. That looks pretty exciting, too in patients who have relapsed. We’re talking about extremely small numbers—anecdotal data—but the drug also has activity as an antibody-drug conjugate.

What’s your experience been like with others out there?

Ian Flinn, MD: You know I think that, we’re also working with other novel antibody-drug conjugates. The issue that I have with them is so far has always been the poison, right? What it’s attached to. And I’m impressed with the neurotoxicity. I’m impressed with the ocular toxicity that can occur with some of these antibody-drug conjugates. So, I’m excited about the class, it makes sense to me. But at the same time, I think there’s a lot of opportunity as people said, a lot of room for improvement there.

John Pagel, MD, PhD: Right. And I think it comes back to this whole conversation about even if we have those in our toolbox, where do they fit in, where does MOR208, a novel Fc-enhanced CD19-targeted antibody, fit in? CAR [chimeric antigen receptor] T cells? And of course 1 patient might not be the same as the next, but in general, I think those antibody-drug conjugates are probably going to be way down the road for treatment encounters. Just because of those toxicities, it can be quite significant.

Ian Flinn, MD: The other drug that I’m excited about is the CD47 drug. You know, 5F9 combined with rituximab. It has a lot of efficacy in [patients with] relapsed/refractory large-cell lymphoma. But the response rates took a little bit of a hit when, after the New England Journal of Medicine publication with many people putting harder patients on the trial. But still, I think as a proof of concept, it’s really exciting and basically a checkpoint inhibitor for the innate immune system. So, I thought that was pretty impressive.

John Pagel, MD, PhD: Yeah, sign me up for that, too. The toxicity or the adverse event profile of the anti-CD47 agents is pretty minimal. People tolerate it well. And it’s another mechanism of action—the “don’t eat me” signals that are inhibited with macrophages. And hopefully, we will have some major rule of how to use those antibodies in the near future. Perhaps the next time we talk in a format like this.

Ian Flinn, MD: Yeah, you can imagine even in combination with some of the therapies that we’ve already talked about. You can imagine that even in combination with MOR208 or lenalidomide, or 1 of the antibody-drug conjugates. I think that would be interesting to pursue.

John Pagel, MD, PhD: Yeah, and just to be complete, you know 1 of the things that we’ve got to look for coming is the pivotal trial that’s being done with tafasitamab, that MOR208, it’s called I believe the B-MIND, the trial. Of, course you have to continue to go with those novel acronyms, but this is 1 where patients are randomized who are not transplant eligible to get bendamustine or rituximab, or to get MOR208 with bendamustine. And that will be an important combination regimen, how we use the antibodies, how to use MOR208 with a cytotoxic chemotherapy. So I’m looking forward to that data upcoming, too.

Ian Flinn, MD: Yeah, that is important data. Well, this has been extremely informative. Thank you, Dr Pagel for this insightful discussion. And thank you to the audience who is watching this Targeted Oncology® presentation on “Targeting CD19 in Diffuse Large B-Cell Lymphoma.” We hope you found this discussion to be useful and informative.

Transcript edited for clarity.

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