Subcutaneous mosunetuzumab-axgb (Lunsumio) has demonstrated clinically meaningful and durable responses in patients with previously untreated B-cell lymphomas, according to interim results from the phase 2 MorningSun trial presented at recent medical conferences. The bispecific CD20-directed CD3 T-cell engager showed promising efficacy across multiple lymphoma subtypes while maintaining a manageable safety profile suitable for outpatient administration.
Strong Efficacy in Marginal Zone Lymphoma
In a dedicated cohort of 36 patients with previously untreated marginal zone lymphoma (MZL), mosunetuzumab achieved an overall response rate of 77.8% after a median follow-up of 18.2 months. Complete responses were observed in 64% of patients, with an additional 14% experiencing partial responses. The median time to response was 2.8 months, and among 30 patients with evaluable tumor responses, 63.9% maintained complete metabolic responses at the time of analysis.
"This is the first study of mosunetuzumab to include a dedicated cohort of patients with previously untreated MZL," said Tara Graff, MD, hematologic oncologist and director of clinical research at Mission Blood and Cancer in Des Moines, Idaho. "Clinically meaningful ORR of 77.8% and a CMR of 63.9% were seen. Durable responses were observed with 18.2 months of median follow-up."
The durability of responses was particularly notable, with both median duration of response and duration of complete response not reached. The 12-month duration of response and duration of complete response event-free rates were 92.3% and 100%, respectively. Median progression-free survival was also not reached, with 6- and 12-month PFS event-free rates of 90.5% and 83.6%, respectively.
Promising Results in High-Tumor Burden Follicular Lymphoma
In a separate cohort of 102 patients with previously untreated high-tumor burden follicular lymphoma, subcutaneous mosunetuzumab demonstrated a 12-month progression-free survival rate of 82.8% after a median follow-up of 13.9 months. The overall response rate reached 87.3%, with 60.8% of patients achieving complete metabolic responses. Among the 89 patients who responded, the median time to response was 2.7 months.
The study enrolled patients who met criteria established by the Groupe d'Etude des Lymphomes Folliculaires for high-tumor burden disease, with most patients (91.2%) having stage III/IV disease under Ann Arbor staging criteria. The median age was 65 years, and 78.4% had a Follicular Lymphoma International Prognostic Index score of ≥2.
Treatment Protocol and Administration
Both studies utilized a fixed-duration subcutaneous regimen designed for outpatient administration. Patients received mosunetuzumab in a step-up dosing schedule, starting with 5 mg on day 1 of cycle 1, followed by 45 mg on day 15, then 45 mg on day 1 of subsequent 21-day cycles for up to 17 cycles. Corticosteroid prophylaxis was mandatory in cycles 1 and 2 to mitigate cytokine release syndrome risk.
In the follicular lymphoma cohort, patients with partial or complete metabolic responses after 17 cycles could receive maintenance therapy consisting of 45 mg every 8 weeks for up to one additional year. As of the data cutoff, 42 patients had received maintenance treatment, with 38 continuing therapy.
Safety Profile Supports Outpatient Use
The safety profile across both studies was consistent and manageable for community practice settings. In the marginal zone lymphoma cohort, all patients experienced at least one adverse event, with grade 3/4 adverse events occurring in 63.9% of patients. The most common adverse events included injection site reactions, fatigue, diarrhea, neutropenia, and cytokine release syndrome.
Cytokine release syndrome occurred in 36.1% of marginal zone lymphoma patients, with all cases being grade 1 (22.2%) or grade 2 (13.9%) in severity. The median time to CRS onset was 2 days, with a median duration of 2.5 days, and all cases resolved. No grade 5 adverse events or immune effector cell-associated neurotoxicity syndrome were observed.
In the follicular lymphoma cohort, injection-site reactions were the most common adverse event (57.8%), followed by fatigue (42.2%), CRS (34.3%), headache (31.4%), and nausea (30.4%). Grade ≥3 adverse events occurred in 44.1% of patients, with serious adverse events in 29.4%. Most patients who experienced CRS had grade 1 severity, with about 5% experiencing grade 2.
Clinical Implications
The results support the potential for subcutaneous mosunetuzumab to provide an effective treatment option for patients with previously untreated B-cell lymphomas in community and outpatient settings. The fixed-duration approach offers a defined treatment timeline, while the subcutaneous formulation eliminates the need for lengthy infusion center visits required by intravenous bispecific therapies.
Dr. Graff noted that the safety and cytokine release syndrome profiles were manageable, "demonstrating that subcutaneous mosunetuzumab can be administered in the US community practices and outpatient settings." The study authors concluded that these data support further exploration of subcutaneous mosunetuzumab in previously untreated follicular lymphoma, particularly in outpatient settings including community and academic centers.
