乌鸦传媒

A of a phase Ib/II trial showed durable responses with mosunetuzumab (Lunsumio) plus polatuzumab vedotin (Polivy) in transplant-ineligible large B-cell lymphoma patients in early relapse or with primary refractory disease. The findings, which had a median follow-up of 2 years, were presented at the recent American Society of Clinical Oncology (ASCO) annual meeting.

乌鸦传媒 brought together three expert leaders in the field for a virtual roundtable discussion: 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. This is the second of four exclusive episodes focusing on the results of the subgroup analysis.

Click here to watch the other videos from this ASCO roundtable series on diffuse large B-cell lymphoma (DLBCL).

Following is a transcript of their remarks:

Nastoupil: We saw some data at this meeting looking at a subgroup of mosunetuzumab in combination with polatuzumab in relapsed/refractory patients. Catherine, what's your take on that study?

Diefenbach: So I'm familiar with this study because I actually participated in this study. So just for all of our listeners here, polatuzumab is an antibody drug conjugate, which is conjugated to a spindle toxin called calicheamicin, just like the brentuximab (Adcetris) drug we were talking about. And polatuzumab targets CD79b, which is ubiquitously expressed on the surface of lymphoma cells. Unlike CD30, which is not very dense on large cells, CD79b is pretty ubiquitously expressed.

So this is basically a chemotherapy delivery system or chemo on a stick. It uses the antibody moiety to target the drug to the cancer cell, hoping to therefore spare the bystander cells that don't have the CD79 the same toxicity and be more direct in terms of the delivery of the chemo. Mosunetuzumab is a really different kind of drug. That's what we call an immunotherapy. It really is an immunotherapy. So it's an antibody that has two arms, and one arm grabs a T cell and activates a T cell. And the other arm, it's the CD3/CD20 bispecific. CD20 is on the surface of almost every malignant B cell in B-cell lymphoma. So CD20 is a very prevalent target. So one arm will target the CD20, the other will target a T cell.

And basically the bispecific antibody says, "T cell, here's a tumor cell, eat it," and brings it into proximity. And the idea is that by basically feeding the tumor to the T cell, you're going to activate all the other T cells. So mosunetuzumab and other bispecifics -- mosunetuzumab is not approved in large cell lymphoma. It's approved in follicular lymphoma in later lines. But two other bispecifics, epcoritamab [Epkinly] and glofitamab [Columvi] are approved in large cell lymphoma. Polatuzumab is approved in combination with bendamustine [Bendeka, Treanda] and Rituxan [rituximab] for more advanced large cell lymphoma.

So in this study, they basically said, let's take really the first bispecific that was developed, which was mosun [mosunetuzumab], and let's take pola [polatuzumab], which is now actually integrated into this treatment of frontline DLBCL and let's combine them and see how they work. And this was a subset analysis looking really at the worst of the worst. So these were patients with either relapsed or refractory disease. And for our listeners, yes, everyone with refractory disease has relapsed, but it's a different category. So people who have refractory disease have relapsed, basically have not responded to chemo or have relapsed within 6 months of chemo. They basically didn't get a benefit from chemo. And patients who are relapsed but have taken longer than that to relapse are considered to have had at least intermediate sensitivity disease.

So what this study showed was that when we looked at the subsets of these very poor acting patients, the combination of mosunetuzumab and polatuzumab was highly active in terms of both CR [complete response] rate and progression-free survival, even for these very high-risk subsets.

Now, if you parse out the relapsed versus the refractory, the difference for the relapsed patients was really no difference from the rest of the population. It was equally good, somewhere in the 70% response rate. The refractory patients had a lower response rate. It was closer to the fifties, but they still had benefit.

I think the take home is if you are treatment-naive to both mosun and pola with large cell lymphoma, then this could be a reasonable option for you. I think it's pretty safe to assume that you're going to be mosun-naive, but in the context of having two other bispecifics approved, I'm not sure why you would go to this over single agent [glofitamab] or [epcoritamab], and you may not be pola-naive if pola is integrated into your frontline chemotherapy.

So I think this is exciting data showing that this regimen is effective even for very poor-risk patients. But again, I'm not quite sure what this is going to mean going forward.

Nastoupil: And Mazyar, how do we sequence this in the setting of a CAR-T? This is going to be post CAR-T, is it going to be an exchange of CAR-T? What are your thoughts about that?

Shadman: So for large cell lymphoma, we now in second line have overall survival advantage of CAR-T therapy over standard of care, which used to be conventional chemotherapy and auto transplant. So I think bringing any other therapy in that space would need a study that shows a significant efficacy advantage or at least non-inferiority. So until we have that in general, in large cell lymphoma, CAR-T remains to be standard of care for patients who are eligible and if they have access to it.

But bispecific therapy in combinations that we're learning more and more about them would definitely be an option for patients who don't have access to CAR-T or in the post CAR-T setting, which is an unmet need in large B-cell lymphoma, it's great to see this promising data.

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