Novel Combination Active in Large B-Cell Lymphoma, Even After CAR-T

Derick Alison
Derick Alison
6 Min Read

A phase Ib/II study demonstrated that mosunetuzumab (Lunsumio) plus polatuzumab vedotin (Polivy) induced durable responses in patients with relapsed or refractory large B-cell lymphoma (LBCL), including patients who relapsed after CAR T-cell therapy. The findings were presented at the recent American Society of Hematology (ASH) annual meeting and simultaneously published in Nature Medicine.

In this final of four exclusive episodes, MedPage Today brought together three expert leaders in the field, all from Ohio State University Wexner Medical Center in Columbus — moderator Kami Maddocks, MD, is joined by Yazeed Sawalha, MD, and David Bond, MDfor a virtual roundtable discussion on the findings from the primary analysis of this ongoing phase Ib/II study. Watch other videos in the series here.

Following is a transcript of their remarks:

Maddocks: All right, so let’s move on to our last abstract. So there’s been a lot of agents approved in relapsed/refractory diffuse large B-cell lymphoma over the last 5 to 6 years. A lot more options than previously, which several years ago would’ve just been chemoimmunotherapy. Lots of interest in these agents in different combinations of novel therapy.

So the last abstract we’ll discuss is the abstract on mosunetuzumab, the CD20xCD3 bispecific plus polatuzumab vedotin, the CD79B antibody drug conjugate. So [Mosunetuzumab] Plus [Polatuzumab Vedotin] Demonstrates a Favorable Safety Profile and Efficacy in Patients with Relapsed or Refractory Large B-Cell Lymphoma: Primary Analysis of a Phase Ib/II Study.

Bond: Yeah, so mosunetuzumab, approved for follicular lymphoma, not approved for diffuse large B-cell lymphoma. It has been studied in that setting, but doesn’t seem to have as high a response rate compared to the two drugs that are approved — epcoritamab [Epkinly] and glofitamab [Columvi]. But also we’ve seen from experience with follicular lymphoma, it’s a very tolerable drug and these bispecifics as a group lend to combination. So I think that’s the setting when looking at these combination therapies, and this was looking at polatuzumab with mosunetuzumab in a fairly large group of patients in this phase II study. So we saw data for other bispecific combinations, but this is a larger study I would say than any of the other ones that were presented. And there was a 62% overall response rate and a 50% complete response [CR] rate.

So I think that the question that comes up is really how does this fit in with knowing that we have two bispecifics approved as monotherapy? And I think without some kind of randomized data, it’s hard to compare directly, but we again tend to see a higher response rate as monotherapy with these two approved drugs. So not entirely clear where this combination fits in, but there is definitely efficacy and I think it just shows that there’s room to build on these bispecifics and look at combinations and so not to just to give those monotherapies moving forward for relapsed disease.

Sawalha: Yeah, I think I found it interesting that polatuzumab did improve the response seen here. So the CR rate was up to 46% by IRC [independent review committee] in this study, which is much higher than what you expect with just [mosunetuzumab] single agent.

But even more interesting to me, that was really the improvement in the risk of CRS [cytokine release syndrome]. It went down from 40 something to less than 18%, so I thought that that was very interesting. I didn’t necessarily expect that kind of improvement in the CRS rate.

Yeah, I’m not sure how would this fit. I mean, I think the improvement in CRS could be of significance. Obviously we’ll need more data to even consider this to potentially be approved or used routinely. But this could help potentially patients in the community where access to large academic centers, where management of CRS might be a challenge, I think that this is potentially a benefit of this regimen.

To make it even a bit more complicated. We know polatuzumab is combined with glofitamab in another clinical trial, and so I think it’s interesting. I think we do need randomization here to be able to make any definitive conclusions here.

Maddocks: And I think of course, it’ll become more challenging as [polatuzumab vedotin] is used more in the front-line setting if patients can receive re-treatment with [polatuzumab vedotin], depending on their time to relapse and all of that.

Alright, Dr. Bond, Dr. Sawalha, this has been a great discussion on some of the abstracts from ASH on diffuse large B-cell lymphoma. Thank you for joining me today for this great discussion.

Sawalha: Thanks for having me.

Bond: Yeah, thank you.

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