Is SC Mosunetuzumab an Effective and Safe Frontline MZL Therapy?

According to recently shared results from the phase 2 MorningSun trial (NCT02500407), single-agent subcutaneous mosunetuzumab (Lunsumio) elicited an overall response rate of 78% in patients with marginal zone lymphoma (MZL), with 14% of patients achieving partial responses and 64% achieving complete responses (CRs). Across various high-risk subgroups, including those with extranodal involvement and those 65 years or older, CR rates were consistent. These results were most recently shared at the Society of Hematologic Oncology 2025 Annual Meeting.

The median time to response was 2.8 months (range, 2.4-5.4). The median duration of response (DOR) and duration of CR (DOCR) were both not reached; 12-month event-free rates of DOR and DOCR were 92.3% and 100%, respectively.

The median progression-free survival (PFS) was not reached (95% CI, not evaluable-not evaluable), with 6- and 12-month event-free rates of 90.5% (95% CI, 73.4%-96.8%) and 83.6% (95% CI, 64.8%-92.8%), respectively.

Concerning safety, any-grade adverse events (AEs) were observed in 100% of patients, and grade 3 or 4 AEs were observed in 63.9%; neutropenia and anemia were the most common grade 3/4 AEs, with rates of 27.8% and 11.1%.

Cytokine release syndrome (CRS) was observed in 36.1% of patients, with no grade 3 or higher events; the median time to CRS onset was 2 days (range, 1-5), and the median CRS duration was 2.5 days (range, 1-7). No events of immune-effector cell-associated neurotoxicity syndrome (ICANS) were reported.

CancerNetwork® spoke with Tara M. Graff, DO, MS, the director of Clinical Research at Mission Cancer and Blood, and the presenting study author, about the results.

Transcript:

What were the most significant efficacy takeaways from the MorningSun trial?

The most significant takeaway was that the median PFS was not reached. Currently, there are about 18 months of follow-up, and that is encouraging when you’re thinking about an indolent disease.

I can speak specifically. I’ve had a few patients, but I have 1 patient specifically on this trial, who finished therapy as of September 2023. She just had her 2-year follow-up scan and last clinical trial visit, and she’s still in a [CR]. She was one of those patients with splenic [MZL]. The…patients with nodal, extra nodal, splenic, and even an unclassified or unknown subtype of MZL were allowed in the trial. Again, patients could have advanced disease, stage III or stage IV for Ann Arbor staging, bulky disease, and higher-risk characteristics. With that median PFS, and with that—what we have right now—18 months of follow-up, specifically for the trial and the way it’s been reported so far, we’ll see updates coming. It’s proving to be not only an efficacious therapy but also a tolerable therapy.

What did mosunetuzumab’s safety profile look like in this trial?

The most common AEs were injection site reactions because it’s a shot. Unfortunately, with any of the [subcutaneous] formulations that we’re using nowadays, that’s always a risk. One thing that is important to point out [is that] yes, [there was] diarrhea and fatigue, [but there was also] neutropenia. We need to be aware of the fact that there are infection risks with using bispecific antibodies, and there were some…higher-grade neutropenic events with mosunetuzumab. [It’s] just something to be aware of. All patients did fine. They weren’t fatal, but you have to be aware of those [AEs]. The elephant in the room was CRS. We know with bispecific antibodies, we have to be aware of CRS, and ICANS or neurotoxicity. Fortunately, there were no ICANS events, and most of the CRS events were all grade 1/2; no grade 3/4 events were seen.

References

Burke JM, Tun AM, Villasboas J, et al. MorningSun: open-label phase II trial of the efficacy and safety of subcutaneous mosunetuzumab as frontline treatment in symptomatic patients with marginal zone lymphoma. Presented at the Society of Hematologic Oncology 2025 Annual Meeting; September 2-6, 2025; Houston, TX. Abstract IBCL-1494.