Mosunetuzumab (Lunsumio) is a first-in-class bispecific antibody that last year received accelerated approval for relapsed or refractory follicular lymphoma.
Atthe recent American Society of Hematology (ASH) annual meeting, longer-term follow-up showed durable responses with the CD20xCD3 T-cell engaging bispecific antibody in the relapsed/refractory setting and another study demonstrated high rates of response with mosunetuzumab as a first-line option for follicular lymphoma patients with a high degree of tumor burden.
In this first of four exclusive episodes, MedPage Today brought together three expert leaders in the field, all from The Ohio State University Wexner Medical Center — moderator Kami J. Maddocks, MD, is joined by Yazeed Y. Sawalha, MD, and David A. Bond, MD — for a virtual roundtable discussion on the encouraging new data at ASH on mosunetuzumab.
Following is a transcript of their remarks:
Maddocks: Welcome to our roundtable for MedPage Today, where we’ll be discussing some abstracts from ASH. We’re going to begin with some abstracts on follicular lymphoma. I am Dr. Kami Maddocks from The Ohio State University James Comprehensive Cancer Center, and I have a few of my esteemed colleagues if you’d like to both introduce yourself.
Sawalha: Hi, I’m Yazeed Sawalha, I’m an assistant professor at Ohio State. Really happy to be here today to talk to you about these, I think, important abstracts.
Bond: Yeah, thank you. And I’m David Bond, so I’m also an assistant professor at Ohio State, also in the lymphoma group. I’m excited to talk about follicular lymphoma and diffuse large B-cell with you today.
Maddocks: Alright, let’s begin with a popular topic. Let’s talk about the CD20xCD3 bispecific mosunetuzumab. So we’re going to discuss a couple abstracts presented at ASH on mosunetuzumab.
Before we discuss these, I just briefly, do either of you have a few words on your experience using mosunetuzumab in relapsed/refractory follicular lymphoma?
Sawalha: Yeah, so I think I’ve used it in few patients. I’ve noticed that really other than the risk of CRS [cytokine release syndrome], it’s very well tolerated. The adverse events are relatively rare in terms of fatigue, nausea, vomiting, things like that. And in my experience in my patients, I haven’t seen any grade 2 or higher CRS. There were only grade 1 CRS that was actually managed outpatient. So overall, very positive experience.
Bond: And just to echo and piggyback off that, I think it’s been really very exciting for our patients that we have this available now and that we’re able to deliver this. And the bispecifics have a lot of attractive features, including that they’re an off-the-shelf treatment that has a high response rate. And I think that the data from ASH really gives us a more granular picture of some of the long-term follow-up and also use in other settings compared to where it’s currently approved.
Maddocks: That sets us up perfectly to discuss the first abstract. So Mosunetuzumab Monotherapy Continues to Demonstrate Durable Responses in Patients with Relapsed and/or Refractory Follicular Lymphoma ≥2 Prior Therapies: 3-Year Follow-up from a Pivotal Phase II Study. So what are thoughts on this abstract?
Sawalha: Yeah, so I think we know they’re active. We know that the CR [complete response] rate is high (60%). I think the question on everyone’s mind is how durable these responses, especially in patients in CR, and this data adds another year of follow-up and it seems that CR in most patients is durable. And so that was really good to see.
So the 3-year PFS [progression-free survival] was 40%. The 3-year time-to-next treatment was, the median was also 3 years. So very encouraging data, I would say, and supports what we hope, all of us hope to see that these CRs are going to continue to be durable.
Bond: And I think in addition to longer follow-up to see how durable the efficacy is, I think there was data on a small number of patients that were actually re-treated after previously responding. And so we saw that at least three to five patients responded to mosunetuzumab re-treatment, which I think is promising for patients who may require treatment again.
And they also did have some data on B-cell recovery after treatment. I think we saw that with this class of treatments, it is a time-limited treatment, so it’s not given indefinitely. And you do see B-cell recovery, but it appeared to be about 18 months from completion of treatment that you see that. So I think that’s important for patients as well.
This is nice that it’s a time-loaded option. And similar to the monoclonal antibodies, I think hopefully you do see recovery over time, which made a difference at least in some cases from other options like CAR-T that we have for the high-risk patients that you’d be considering the bispecifics for.
Maddocks: I think that’s a great point about the re-treatment. There were only a few, a small number of patients re-treated, but it was nice to see that patients were re-treated and achieved complete responses with their re-treatment. And I think that’ll be important as we potentially move this into earlier lines of therapy.
Which kind of brings us to hit on the second abstract, which is Subcutaneous Mosunetuzumab As First-Line Therapy for Patients with High Tumor-Burden Follicular Lymphoma: First Results of a Multicenter Phase 2 Study. So thoughts on this abstract?
Sawalha: Perhaps the one thing I first thought about is, are we going to see a higher risk of CRS in patients who are previously untreated? You always worry about that — and patients who [have] never been exposed to chemotherapy. And fortunately these data don’t show higher risk of CRS. So most of the events were grade 1. The risk of actually grade 2 CRS was very low, only 4% and no grade 3 or 4 CRS events. Almost all patients were managed outpatient except for the two patients who had grade 2 CRS. So that was very reassuring to me that the CRS, the toxicity, didn’t seem to be excessive in this patient population.
And then the other point, the CR rate was quite remarkable (76%), so that’s very high. Hopefully — we’ll definitely have to wait — but hopefully the CR will also be durable in this setting.
Bond: And the one caveat, it’s a small number of patients on this study, so the complete response rate and the overall response rate, I think you have to take that into consideration that with more patients you may get a better sense of the true efficacy. But very promising. And potentially when you’re using these treatments earlier on in treatment, you have patients that have differences in their tumor biology and also maybe a more intact immune system without prior chemoimmunotherapy, and so you may see more efficacy.
So I thought it was very promising to see how high the overall and complete response rate was for the treatment-naive patients, particularly with high tumor burden with just a single agent bispecific antibody.
Maddocks: Yeah, I thought that was great. And I agree with Dr. Sawalha. I mean the CRS was pretty similar to what was seen in relapsed/refractory study.
Sawalha: I thought it was also interesting the data they presented on CD20 loss actually — in just three patients, so very small number of patients — but those patients on progression, they lost the expression of CD20 by IHC [immunohistochemistry].
There are also some data we know from large B-cell lymphoma also shows that this is one mechanism of resistance, or progression to the CD20 bispecific antibodies.
Maddocks: Yeah, so look for more on those in follicular lymphoma.
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Publish date : 2023-12-20 14:30:49
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