Targeting CD19 in Diffuse Large B-Cell Lymphoma - Episode 3

CD19-Targeted MAbs in Relapsed/Refractory DLBCL

Targeted Oncology

Ian Flinn, MD: Well, let’s spend some time talking about a therapy in development for patients with large-celllymphoma—relapsed and refractory T-large cell lymphoma. Tafasitamab, otherwise known as MOR208, is an SE-engineered humanized CD19 monoclonal antibody. Specifically, it’s been engineered to have better ADCC [antibody-dependent cellular cytotoxicity] than a native antibody. It’s been going through several clinical trials. And so I think that this is an exciting new therapy.

John, what’s your take on MOR208? The data coming out are pretty exciting in terms of the data seen in large-cell lymphoma when combined with lenalidomide. Do you think we’re really improving the ADCC with this antibody, or is it just the design of the trial?

John Pagel, MD, PhD: Yes, it’s a good question. I’m glad we’re not going to keep saying tafasitamab, but we’ll call it MOR208, as you suggested, so thank you for that. I’m excited about this drug. It’s a real drug. It’s a real antibody. It’s definitely showing very encouraging data, as you mentioned. It’s a little different as an antibody, perhaps. It’s an Fc-humanized monoclonal antibody. So because of that humanized portion—that Fc-humanized portion—that perhaps it provides greater antibody-dependent cellular cytotoxicity, or ADCC. Certainly, the preclinical data support that. We know it’s clinical activity in relapsed large-cell lymphoma when you combine it with lenalidomide—as you mentioned—appears quite encouraging. And I think the FDA kind of looks at it that way, too because they’re granting an accelerated approval pathway for that combination of MOR208 with lenalidomide.

Ian Flinn, MD: I’m impressed as well. We worked with it a number of years ago in the first-in- human studies in patients with CLL [chronic lymphocytic leukemia]. And it was clearly an effective antibody. This was prior to BTK [Bruton tyrosine kinase] inhibitors and some of the new targeted therapies. And so I think the challenge was, as those that were coming in, how to really develop it in that era.

But the MOR208 investigators have done a great job of trying to build upon this engineered CD19 antibody that has augmented ADCC. They have combined it with lenalidomide, an immune-modulating agent. I think that was brilliant, and we are trying to build upon its strength engine and bring it into patients with large-cell lymphoma.

Transcript edited for clarity.