ASH 2025 | Fixed-duration SC mosunetuzumab in older patients with previously untreated DLBCL: MorningSun trial

I had the honor of presenting the results of the Phase II MorningSun study on behalf of my colleagues. And this was a basket study for looking at the treatment effect and safety of mosunetuzumab in various different cohorts of lymphoma patients. This included follicular lymphoma, large cell lymphoma, marginal zone lymphoma, and several relapse indications. But my presentation was focused on the treatment of elderly, treatment-naive, diffuse large B-cell lymphoma. The challenge in this population is that the standard of care is probably R-CHOP or R-mini-CHOP chemotherapy, but that’s hard to administer in patients who are age 80 or above or have medical comorbidities. Or I should say, it is the standard in that population as much as there is a standard, but many patients in that age group aren’t able to get the therapy or there’s a lot of treatment-related adverse events. 

And so this was looking at mosunetuzumab instead administered as a single agent. This was given on days 1, 8, 15 of cycle 1, followed by once every three weeks. It was administered subcutaneously in the outpatient setting. There was no mandatory hospitalization for this. And we enrolled an older population. The median age was 82. The range was 76 to 101, so we had some old patients on this study. 

And what we saw was that we had very favorable response rates. The overall response rate was near 70%. About half of patients had a complete response. Those complete responses were associated with MRD negativity in many patients. And what we saw, at least with 12 and a half months of median follow-up, was that those responses appeared durable. Now, I will say that 12 and a half months is early, so we need to follow these patients. But at least in prior studies, what we’ve seen is that patients who achieve complete responses can oftentimes do quite well with very durable responses. 

In terms of safety, you know, this is obviously going to be one of the really important areas to consider for this population. One of the drug class effects that we frequently can see is cytokine release syndrome, and so that was the area that we paid particular attention to. We did use dexamethasone prophylaxis. We did not use tocilizumab. They were free to use it, but there was no prophylactic tocilizumab. Cytokine release was only seen in 12% of study subjects, and it was grade one in all but one patient, where it was grade two. This occurred early, typically within the first 24 to 48 hours after the first dose, and resolved in all patients. One of the concerning side effects sometimes seen in this population is what we call ICANS, which is Immune Cell-Associated Neurotoxicity Syndrome. And that can present as confusion, progress to stupor, headache, you know, a lot, it can be quite problematic. We did not observe that in any study subjects on our study. In terms of other side effects, injection site reactions, a little bit of fluid retention, we certainly saw infectious complications. This study did take place during COVID, but we didn’t have a whole lot of COVID on the study. There were some pneumonias and so forth. But overall, I think a very well-tolerated therapy for this population. 

One of the really exciting things during the session, because there were actually several presentations that were very similar in design, is there really does appear to be an appetite to get rid of R-mini-CHOP in elderly large cell lymphoma. Now, I don’t think we’re there yet. I think we need to ideally design a head-to-head study that would compare a bispecific approach, perhaps with an antibody-drug conjugate, and compare it directly against R-mini-CHOP. And I think that we’re likely to see such a study in the coming months and years.

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