Targeting CD19 in Diffuse Large B-Cell Lymphoma - Episode 6
Ian Flinn, MD: When we talked earlier, we thought this was a pretty brilliant design. I mean, there’s another study that’s called Re-MIND. So Re-MIND is where the MOR208 investigators are basically looking at the case control series where nearly 500 patients treated with single-agent lenalidomide was compared to what happened to patients in the L-MIND study—the study that we’ve just been mentioning.
And so, they really took a huge group of patients and were able to do very careful matching between the 2 different studies. And in that study, it really looks like that L-MIND, the combination with lenalidomide and MOR208, a novel Fc-enhanced CD19-targeted antibody, did much better than the control lenalidomide. And so I think it’s brilliant because it would never occur to me that in the past, that this was a possibility of using this kind of real-world data to use as a control for patients and get a therapy approved through the FDA. So, I thought that was really exciting news. I think it opens up a lot of opportunities in drug development in general, not just for this drug but trying to use real-world data.
Many people have argued that these retrospective real-world populations are actually much more important than what we’re seeing in clinical trials because they reflect a much broader group. Now, in this case, they narrowed it down to make people that had to be sensor patients that were eligible for the L-MIND study in order to be the control group. But what did you think about the first time you heard about this, John?
John Pagel, MD, PhD: Yeah, this was actually fantastic. This really was something we should be doing all the time—at least looking at real-world data. I don’t know what the real world is, but when you’re identifying 500 patients who got single-agent lenalidomide in relapsed/refractory large-cell lymphoma, these are people that obviously don’t have great options because they’re getting this off-label use. It’s got to be meaningful—and as long as you can compare adequately.
So, you’re right, they did compare the 81 patients in the L-MIND trial to about 80, 81 patients who were identified that were well matched. There’s always, of course, biases and flaws there that are probably inherent. But nonetheless, as you said, the data clearly showed that the responses were inferior to single-agent lenalidomide. They was only an overall response rate of about 40%. Remember in the L-MIND trial, it was about 60%—maybe even a little bit more.
And the CR rate, or the complete remission rate for those people who just got single-agent lenalidomide was about 10% or 12%. And in the L-MIND trial it was I think 33%. So it’s kind of hard to argue that those big differences are not significant in my mind. And if you’re going to be thinking about trying to salvage someone with a lenalidomide-based regimen, maybe this is a new federal alternative.
So, I was actually really encouraged by it. But maybe even more, and I’m wondering, you know, in a real-world comparison retrospective analysis, if this is valid or not, but that data showed that there was an overall survival advantage for the people that got MOR208 with the lenalidomide, compared to lenalidomide alone.
I don’t know if that’s going to play out in a prospective approach. We know that there’s a lot of different factors that go into how people deal with overall survival. But, do you agree? I mean, that seems like a pretty exciting thing if you ask me.
Ian Flinn, MD: I do think this is a significant difference. I’m reminded of the data with elotuzumab in combination with ER, that the difference, the numbers are really quite small. The number of people that actually benefited were small in comparison to this larger dataset in the L-MIND study and combining it and comparing it to the Re-MIND data. So, I think it’s in practice.
We will have to see a confirmatory trial, I’m sure, ultimately in the future—probably moving this therapy in a front-line setting in combination with R-CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone, plus rituximab]. And so, I think that’s going to be a very important ultimate confirmatory trial and outcome. Ultimately, we like to move things forward in our therapy for large-cell lymphoma because that’s where the real difference is.
The other thing I’m impressed by is that this therapy seems to be different than other CD19 antibodies. There’s a couple publications with MEDI-551, looking in combination at some of the salvage regimen for relapsed large-cell lymphoma. And in that case, it’s really no different than the rituximab-containing regimens. And so that seems different to me.
John Pagel, MD, PhD:Yeah, but that’s early data. We’ll see what that shows. It’s a different approach. Maybe there will be some important advances there. I would say the enthusiasm for anti-CD19 antibodies is very high, and I hope we do continue to develop other therapies in that regard.
Transcript edited for clarity.