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A three-drug combination consisting of the antibody-drug conjugate brentuximab vedotin (Adcetris) plus lenalidomide (Revlimid) and rituximab for diffuse large B-cell lymphoma (DLBCL) improved survival in the third-line setting versus lenalidomide plus rituximab (R2) alone, according to an interim analysis of a phase III study presented at the American Society of Clinical Oncology (ASCO) annual meeting.

番茄社区app brought together three expert leaders in the field: Moderator , of the University of Texas MD Anderson Cancer Center in Houston, is joined by , of NYU Langone's Perlmutter Cancer Center in New York City, and , of the Fred Hutchinson Cancer Center in Seattle, for a virtual roundtable discussion. This is the first of four exclusive episodes focusing on the ECHELON-3 study.

Following is a transcript of their remarks:

Nastoupil: Hi, I am Loretta Nastoupil from the University of Texas MD Anderson Cancer Center, and we're going to have a roundtable discussion on updates from the 2024 ASCO meeting. And it's a real privilege to have my colleagues with me. Mazyar, go ahead and introduce yourself.

Shadman: Yeah, great to be here. My name is Mazyar Shadman. I'm from Fred Hutch, University of Washington, in Seattle.

Nastoupil: And Catherine.

Diefenbach: Hi, I'm Catherine Diefenbach. I'm from the Perlmutter Cancer Center at NYU Langone Health.

Nastoupil: Let's jump right in. So what's changed for large cell lymphoma at this meeting? So starting in the relapsed setting, we saw some studies read out, particularly some newer targeted therapies. And, Mazyar, what are your thoughts about the ECHELON-3 study?

Shadman: Yeah, so we saw some interesting data from an antibody-drug conjugate that we are familiar with in lymphoma, but in Hodgkin lymphoma and T-cell lymphoma. And these study investigators compared the combination of brentuximab vedotin with rituximab and lenalidomide compared to rituximab and lenalidomide. And in the relapsed setting, they reported improved efficacy with the combination, including an overall survival advantage. Now this is an anti-CD30 antibody-drug conjugate, not a target that we commonly think about in large cell lymphoma, but the data look interesting and have created some discussion at the meeting.

Diefenbach: I think it's interesting because CD30 as a target in large cell is not really something that you think about as a very relevant target. And, in fact, when Seattle Genetics, they did several studies in large cell lymphoma trying to show that brentuximab had activity in large cell as a single agent. And it had some activity, but it was nothing to get an approval with. And then they tried to parse it and look at whether you were a CD30 high expressor, you had more, it was a more active drug. And the take-home seemed to be that, yes, the density of CD30 expression did impact response a little bit, but again, it wasn't overwhelming enough to get it approved.

Now, if I have a patient who is large cell who no longer expresses CD20 and has CD30, would I potentially give them brentuximab? Sure. And I actually have done that to a patient recently.

But I think what's really odd to me about this study is I don't really understand how it was designed. So while R2, which is lenalidomide and rituximab, is a highly active and approved agent for follicular lymphoma, and it's a standard of care for relapsed follicular lymphoma, and it is active in large cell, it is not an approved regimen in large cell. So you're taking a drug that is not approved in large cell lymphoma, adding it to two other drugs that are not approved in large cell lymphoma, and showing that that's better than the combination of the two drugs that are not approved.

But I don't see an approval pathway forward, whatever the data are, and we can certainly parse the data. I think there are some surprising things in the data in terms of how the standard arm did, but I don't really see a path forward. What do you think, Loretta?

Nastoupil: It's interesting. I don't think of brentuximab having synergism with lenalidomide-rituximab, but clearly it had some additive activity in a disease where we're really looking for some active agents. But I agree it's going to be challenging to know how to put this into context with the other options. And then do they have to do another randomized phase III against a standard-of-care arm to really know how it impacts the treatment landscape?

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