Subcutaneous Mosunetuzumab Induced High Response Rates in First-Line MZL

Administration of subcutaneous mosunetuzumab (mosun SC), a CD20xCD3 bispecific antibody, led to high overall response rates (ORR) and complete metabolic response rates (CMR) in patients with previously untreated marginal zone lymphoma (MZL). Findings from a phase II study were presented by John M. Burke, MD, of Rocky Mountain Cancer Center in Aurora, CO, at the EHA 2025 Congress in Milan, Italy.

Currently, mosunetuzumab is approved as a fixed-duration intravenous therapy for relapsed/refractory follicular lymphoma. The open-label MorningSun trial (NCT05207670) is the first to evaluate the efficacy and safety of the subcutaneous formulation in patients with first-line MZL. Thirty-six patients with symptomatic splenic, nodal, or extranodal MZL were enrolled, with a median age of 69 years (range=36-81). Seventeen percent of patients presented with B symptoms. Mosun SC was administered with step-up dosing in cycle 1 (5mg on day 1, 45mg on days 8 and 15), followed by 45mg on day 1 of each 21-day cycle for up to 17 cycles or until disease progression or unacceptable toxicity. Hospitalization for cytokine release syndrome (CRS) monitoring was not required.

Common adverse events (AEs) included injection-site reaction (69%), fatigue (56%), headache (33%), cough (33%), anemia (31%), and diarrhea (31%). Grade ≥3 AEs were reported in 61% of patients, primarily neutropenia (28%) and anemia (11%). Infections were reported in less than 10% of patients, and included COVID-19 (22%), sinusitis (14%), pneumonia (11%), and urinary tract infection (11%). Thirteen patients (36%) experienced low-grade CRS with a median onset of 2 days post-dose and lasting a median of 2.5 days. All CRS events were resolved, having been managed with tocilizumab (n=5), steroids (n=5), both (n=2), or supportive care (fluids n=5, low-flow oxygen n=1). No fatal AEs were reported.

The primary endpoint of the study was ORR, defined as partial or complete metabolic response. After a median follow-up of 11.3 months, the ORR was 75% (n=27, 95% CI:58-88), with a CMR rate of 61% (n=22, 95% CI: 44-77). At the time of data cutoff, 61% of patients remained in CMR. Median time to response was 2.8 months (range, 2.1-5.4) and median number of cycles was 14.5 (range, 1-17). A total of 10 patients (28%) completed the full 17 cycles, 13 continued treatment, and 13 (36%) discontinued due to AEs (11%), physician decision (8%), progressive disease (8%), patient withdrawal (6%), or were lost to follow-up (3%).

Compared to intravenous mosunetuzumab, mosun SC offers similar efficacy with manageable CRS. In addition to the absence of mandatory hospitalization and the ability to administer mosun SC in community outpatient settings, these results support further investigation of mosun SC as an off-the-shelf therapy for first-line MZL, researchers concluded.