What Direction Should Marginal Zone Lymphoma Research Be Heading?

At the Society of Hematologic Oncology 2025 Annual Meeting, Tara M. Graff, DO, MS, presented updated results from the phase 2 MorningSun trial (NCT02500407) that showed subcutaneous mosunetuzumab (Lunsumio) yielded durable responses as a frontline therapy for patients with marginal zone lymphoma (MZL).

After the presentation, Graff, the director of Clinical Research at Mission Cancer and Blood, spoke with CancerNetwork® about the results. When prompted about the most promising paths forward for frontline MZL care, she emphasized combination therapies.

In MorningSun, a total of 64% of patients achieved complete responses (CRs) while receiving mosunetuzumab. Additionally, with 18 months of follow-up, the median progression-free survival (PFS) was not reached.

She did note that there is an increased risk of adverse events (AEs), such as cytokine release syndrome (CRS) or long-term infections, when adding a partner to mosunetuzumab; in the trial, single-agent mosunetuzumab did not lead to any instances of grade 3 or higher CRS.

Transcript:

Combination [therapies are the next step in MZL]. Eventually, once we know that single-agent mosunetuzumab maintains its efficacy over time—that’s always the big thing, you can have overall response rates, and initial PFS and interim analysis that look good, but you need to maintain that over time. If it does continue to do that, then [we question] “Okay, does it need a partner?”

When you add a partner, you increase the risk for more [AEs]. Not just the CRS and neurotoxicity—again, neurotoxicity is not happening in the [patients with] MZL, but that’s just fleeting, and that’s just the first cycle—but the long-term infections and things like that. If single-agent [rituximab] was good enough for all these years, for MZL, I don’t know if you have to put something with it. Is it going to be mosunetuzumab with a BTK inhibitor? I don’t know. They’re looking at zanubrutinib [Brukinsa] in [MZL]. Will you have mosunetuzumab and zanubrutinib? Do you need that? Is that more of a second-line therapy? Do you need an extra drug [in the] front line? We don’t know. [MZL] is not something like [diffuse large B-cell lymphoma] and follicular [lymphoma], that we’re talking about constantly. It sits over here like the stepbrother. They’re all good questions. From the talks we’ve seen today, [there are] a number of combination bispecific [antibody] trials, but I just don’t know how much we’re going to do that, or how quickly we’re going to do that, in [MZL].

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.