A Closer Look at the Potential Impact of Bispecific Antibodies on the DLBCL Treatment Landscape


Physicians speculate on the potential impact of bispecific antibodies on the treatment landscape of DLBCL.

Grzegorz S. Nowakowski, MD: Will bispecific antibodies replace CAR [chimeric antigen receptor] T-cell therapies too?

Leo Gordon, MD: I thought Michael Dickinson’s report [at the American Society of Clinical Oncology Annual Meeting] was impressive. I didn’t expect to see that.

Frederick Locke, MD: Do you think it would replace CAR, though?

Leo Gordon, MD: I don’t know. I never thought it would.

Matthew Lunning, DO, FACP: Are you speaking to the glofitamab data? Is that what you’re referencing?

Leo Gordon, MD: Yes. I was more impressed than I thought I’d be.

Matthew Lunning, DO, FACP: The median PFS [progression-free survival] was still 4.9 months. It has the baggage of obinutuzumab along with it. Granted, it’s 1 dose. I see it as a shepherd that replaces polatuzumab rather than a replacement of CAR T cell.

Leo Gordon, MD: I can easily see that.

Grzegorz S. Nowakowski, MD: The biggest advantage of bispecific antibodies is that you can combine it with other therapies at the same time. Those combinations appear to be quite feasible. The response rate is quite impressive. With already long follow-up, those responses appear to be durable from the initial studies and in combinations.

Matthew Lunning, DO, FACP: What was amazing across the board, whether it’s glofitamab, mosunetuzumab, epcoritamab, or all the other bispecifics coming, is the non-hematologic toxicity. I often think that if I’m going to use it as a shepherd to cellular therapy, I’m looking for non-hematologic toxicity, like grade 3 to 4. I want disease stabilization without ECOG migration—meaning from 1 to 3 in ECOG score—so that when I’m doing lymphodepleting chemotherapy, my colleagues aren’t looking at me like, “Really?” That has an adverse event profile that satisfies me. I couldn’t care less about their temporary neutropenia or fever that they also had when they got their COVID-19 shot. It’s going to find its place. The real question is: if you get them to into a CR [complete response], then what do you do? Because that’s where there could be a potential for durability.

Frederick Locke, MD: Yes, the data were impressive with glofitamab, and that’s a therapy that’s probably going to end up as part of our standard-of-care armamentarium based on the data. But when I look at it, I don’t see it as a replacement for CAR T. I see a 35%-to-38% CR rate. For patients who had a CR, it’s very durable. At 2 years, 60% of them are still in remission. But 60% of 35% isn’t comparable with CAR T cell therapy. I wouldn’t think—at least in this current iteration—that it’s going to replace CAR T, but how we’re going to use it is an open question.

Leo Gordon, MD: About a third of the patients had prior CAR T and responded. But we don’t know the duration of that response in the post–CAR-T setting either. We didn’t have those data.

Matthew Lunning, DO, FACP: They may have been driving some of the hematologic toxicities that were reported too, so it’s going to be very important to follow those data and watch it dichotomize between pre–CAR-T and post–CAR-T patient populations.

Frederick Locke, MD: I have 1 more thing to follow on your toxicity comment. Yes, the hematologic toxicity seem reasonable, but there was CRS [cytokine release syndrome] in that glofitamab data set, and it was 60% within the first few weeks. There was even a subset of almost 10% grade 2 CRS. We have to think about that in terms of how we administer those therapies and do it safely, whether that can eventually be done in the community or if this can be a therapy that’s done in sites like ours. But after the first month or so, it seems as if all those toxicities [dissipate].

Matthew Lunning, DO, FACP: It makes me wonder what we would call this fairly predictable fever and hypotension that’s responsive to fluids if this class of therapy was developed outside a CAR T cell. What would we call it in the prior pre–CAR T-cell arena? First-dose rituximab [Rituxan] infusion—

Leo Gordon, MD: First-dose Rituxan. It’s another antibody.

Matthew Lunning, DO, FACP: It’s a balance that we’ve shepherded CRS into this space. But is it really CRS?

Frederick Locke, MD: Is it the same CRS?

Matthew Lunning, DO, FACP: Is it the same CRS?

Frederick Locke, MD: You can stop it, right?

Leo Gordon, MD: The close part is that there are T cells involved, and that might even be true with Rituxan.

Matthew Lunning, DO, FACP: It has also been interesting to see how much tocilizumab is being used in this space and what a grade 1 or 2 CRS after a bispecific looks like.

Transcript edited for clarity.

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