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Positive Results for Odronextamab in Relapsed/Refractory DLBCL

— But experts aren't sure where it would fit in with currently approved bispecifics

Ƶ MedicalToday

, the investigational bispecific antibody odronextamab demonstrated clinically meaningful efficacy in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), according to research presented at the recent American Society of Hematology (ASH) annual meeting.

In this first of four exclusive episodes, Ƶ brought together three expert leaders in the field, all from The Ohio State University Wexner Medical Center in Columbus -- moderator , is joined by , and -- for a virtual roundtable discussion on the ELM-2 study's final results.

Following is a transcript of their remarks:

Maddocks: Welcome to our MedPage ASH roundtable where we will be discussing abstracts out of ASH from diffuse large B-cell lymphoma. I'm Dr. Kami Maddocks from The Ohio State University James Comprehensive Cancer Center, and I have with me a few of my esteemed colleagues. If you guys would like to introduce yourselves.

Sawalha: I'm Yazeed Sawalha, an assistant professor at The Ohio State University. Very happy to be here with you today to discuss these interesting abstracts.

Bond: Yeah, thank you. And I'm David Bond. I'm also at Ohio State University as an assistant professor and I'm excited to talk today about diffuse large B-cell and updates from ASH.

Maddocks: Alright, let's get started. So we're going to start with an abstract on a hot topic -- bispecific antibodies. So we've seen the approval of two different CD20xCD3 bispecific antibodies in relapsed/refractory diffuse large B-cell lymphoma within the past year, and out of ASH we saw results on a third one. So final analysis of the phase II ELM-2 study, odronextamab in patients with relapsed/refractory diffuse large B-cell lymphoma.

Maybe you guys could just comment a little bit about bispecific antibodies in your practice in general, and then on this abstract in particular.

Bond: Yeah, yeah, like you said, Dr. Maddocks, so bispecifics are certainly, I think, the hot topic in diffuse large B-cell lymphoma right now. And we have two drugs that have been approved in the past year with glofitamab [Columvi] as well as epcoritamab [Epkinly]. And there was another drug that I think may have fallen behind in the development process somewhat, but odronextamab, which was actually among the first to be studied in diffuse large B-cell lymphoma in this class.

So yeah, these are exciting therapies that are off-the-shelf. They target CD20, similar to rituximab with monoclonal antibodies, but also have an arm to target CD3 and to help introduce an immune response. And it's been exciting to see this proof of principle to be effective and to have now these treatments to offer. And I think that we, yes, are using them in practice as standard of care fairly often now for patients with relapsed disease, particularly after CAR-T [chimeric antigen receptor] therapy.

Sawalha: Yeah, I agree. Very exciting drug, very effective. Probably our preferred third-line treatment option for most patients, especially in the post-CAR-T setting.

Bond: And so the update at ASH that we were discussing here for the ELM-2 study was with odronextamab. And it was a large study, it was with 127 patients that were efficacy-evaluable -- there were actually more patients that were safety-evaluable -- and it was looking at multiple different dosing schedules over the course of the study, but they presented the final results from the study overall.

I think as far as the safety, that has been one of the reasons that it may have slowed the development, it was finding a dosing schedule that works for this drug. The final dosing schedule that they did land on when that was studied in 74 patients, the incidence of CRS [cytokine release syndrome], while the incidence was fairly high, it was almost all grade I/II, so it was 98% grade I/II CRS with the final dosing schedule. So I think that's reassuring and so that's something that is feasible to see in practice and to use.

And at the final of the efficacy-evaluable patients, at the final last point, the overall response rate was 52% with a complete response [CR] rate of 31%. So certainly that's better than a lot of the therapies we had in the past for large B-cell lymphoma. I think when you look at -- there's currently two approved drugs for large B-cell lymphoma, and it's hard to compare directly -- but you see that those currently approved drugs have at least similar response rates, but actually numerically at least higher overall and complete response rates.

I think that's one of the questions is where does odronextamab fit in really with the current approved drugs, given the same mechanism of action, same class of therapy. But still good to see the final results of this study. And it's a large study and shows proof of principle with a third drug in the bispecific class for this disease.

Sawalha: Yeah, I agree with you. I also am not clear how it's going to fit, especially as we have the other two bispecific antibodies approved. And I think it's also important to highlight that in this study, in the ELM-2 study, patients with prior CAR T cells were excluded. And we know that the outcomes, even with the bispecific antibodies in this patient population tend to be slightly worse. So the CR rate here was 31%, but again, excluding patients with prior CAR T cells.

And the safety data, I agree with you also, looks like it's better now with the step-up dosing, which the other bispecific antibodies are also using. So kind of interesting data, good data, but I'm not sure how the drug would fit in the treatment paradigm given the two other bispecific antibodies.

Maddocks: I think the other thing about this is just kind of the treatment schedule, the frequency of infusion, continuation of therapy and...

Sawalha: Less convenient than the other two ones.

Maddocks: Yeah.

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    Greg Laub is the Senior Director of Video and currently leads the video and podcast production teams.