Targeting CD19 in Diffuse Large B-Cell Lymphoma - Episode 7

CD19 and CD20 Antibodies in Development

Targeted Oncology

Ian Flinn, MD: Both the CD20 and CD19 antibodies—mosunetuzumab, I think we’ve been working with that, I think that’s an impressive antibody. That tolerability of mosunetuzumab is actually pretty good. We’ve worked in the past with a CD19 bispecific frankly, and it was worse than CAR [chimeric antigen receptor] T cells. And so, I don’t know whether that was specifically that product in and of itself, but because the CAR T cells were targeting CD19 and this one was targeting CD19 and still using an IMiD [immunomodulatory imide drug]therapy, we saw a lot of adverse events and ultimately, that trial had to be stopped.

So clearly, not just a CD19 in and of itself, we don’t see that with MOR208, a novel Fc-enhanced CD19-targeted antibody]. It’s an immunotherapy for some reason that seems to be causing that problem. But as a class, I’m very bullish on bispecifics. I think there’s a great deal of excitement with that group of antibodies. We’re testing several in our program.

John Pagel, MD, PhD: Yeah, and I’ll just say I’m bullish on them as well. I’m bullish on tafasitamab, too because that agent, these bispecifics are off the shelf, right? We can get them to patients right away. It’s not something we can do with the CAR T-cell treatment as we discussed early on in the program.

Ian Flinn, MD: Yeah, I think 1 of the very important parts here is that you can give it quickly to people with a good tolerability. That’s true with both MOR208 as well as some of the new bispecifics that are coming around. Go ahead John.

John Pagel, MD, PhD: And of course, don’t forget, I’m sorry to interrupt you there, but I do think it’s important that we have to remember that the bispecifics, which you’ve been alluding to, also have significant toxicity and can have CY10 release and other toxicities like we see with CAR T-cell treatment. And again, we’re not seeing that with the tafasitamab or the MOR208. So, bispecifics are encouraging. I’m bullish on them as we said. They’re off the shelf. But they are potentially very toxic in some patients.

Have you used blinatumomab in patients with large-cell lymphoma? It’s indicated in ALL [acute lymphoblastic leukemia]. It had some of the same toxicities that we’ve been talking about,

neurotoxicity and so forth. But I haven’t really used it in patients with large-cell lymphoma. It’s very cumbersome to give.

Yeah, I think that’s the problem, right? It’s hard to deliver, and the toxicity of that drug can be very significant. These people have to be in the hospital for a significant amount of time, not uncommonly. And the activity is not great, so I’m not a large user. In fact, we are really almost never using that in this space. We have other drugs now, as we’ve been talking about.

Transcript edited for clarity.