Clinically meaningful and durable response of mosunetuzumab in MZL

The first study of mosunetuzumab in a dedicated cohort of patients with treatment-naive marginal zone lymphoma (MZL) resulted in clinically meaningful and durable responses after 18 months of follow-up. Safety and cytokine release syndrome (CRS) profiles were manageable.

Mosunetuzumab is a CD20xCD3 bispecific antibody, offering a fixed-duration treatment that can be administered in the outpatient setting. Mosunetuzumab is already approved for the third-line treatment of patients with refractory or relapsed follicular lymphoma (R/R FL). Dr Tara Graff (Mission Cancer and Blood, IA, USA) reported the efficacy and safety results of subcutaneous (SC) mosunetuzumab as frontline treatment in symptomatic MZL patients in the open-label Phase II MorningSun trial (NCT05207670) [1] at the 13th Society of Hematologic Oncology (SOHO) 2025 Annual Meeting in Houston, TX.

Patients had splenic, nodal and extranodal, previously untreated, symptomatic MZL. To mitigate the cytokine release syndrome (CRS), step-up dosing was applied in the first cycle, and corticosteroid prophylaxis was mandatory in cycles 1 and 2. Patients were treated for up to 17 cycles. The primary endpoint was investigator-assessed overall response rate (ORR) according to the Lugano Criteria.

A total of 36 patients were included. The median age was 69 years; 75% of patients were male. 28 (78%) had extranodal involvement. As Dr Graff explained, the median follow-up was 18.2 months. The median number of cycles received was 17; no patients remained on therapy. Of 36 participants, 21 (58.3%) completed the treatment. Of the 15 patients who discontinued mosunetuzumab SC, adverse events were the reason in 6, and disease progression in 3. The ORR was 78% (complete response: 64%). In the group with extranodal involvement, the ORR was 82%, in patients younger (n=12) and older (n=24) than 65 years, it was 92% and 71%, respectively. In patients with Ann-Arbour stage I/II (n=11) and III/IV (n=25), ORR was 100% and 68%, respectively. Median time to response was 2.8 months. At the time of analysis, 23 patients (63.9%) still had complete metabolic response (CMR).

Side effects included low-grade CRS, injection site reactions and infections. Infections were mainly low-grade and manageable; there were no fatal infections. Dr Graff concluded that, in all, these results support further exploration of mosunetuzumab in patients with previously untreated MZL.

1. Graff T, 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 (MZL). SOHO 2025, 2-7 September 2025.

Medical writing support was provided by Dr Rachel Giles.
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Posted on 19 September 202519 September 2025