Subcutaneous Mosunetuzumab Shows Durable Responses in Relapsed/Refractory Follicular Lymphoma

Key Clinical Summary:  

• Subcutaneous (SC) mosunetuzumab met pharmacokinetic noninferiority criteria compared with intravenous (IV) mosunetuzumab and produced an overall response rate (ORR) of 76.6% and a complete response (CR) rate of 61.7%.
• Median progression-free survival (PFS) reached 23.7 months, and median duration of complete response (DOCR) was 34.6 months with SC administration.
• Cytokine release syndrome (CRS) occurred in 29.8% of patients receiving SC mosunetuzumab and was predominantly grade 1 or 2, suggesting the formulation could provide an alternative route of administration while maintaining efficacy.

Subcutaneous administration of mosunetuzumab demonstrated pharmacokinetic noninferiority to the intravenous formulation while producing durable responses in patients with relapsed/refractory follicular lymphoma (R/R FL), according to results from a clinical study comparing the 2 formulations. The findings may have implications for treatment delivery as bispecific antibodies become increasingly incorporated into the management of R/R FL.

Investigators evaluated the pharmacokinetics, efficacy, and safety of a 45-mg SC dose of mosunetuzumab compared with the 30-mg IV formulation. Among 94 patients treated with SC mosunetuzumab, response rates and survival outcomes were similar to those previously observed with IV administration.

Subcutaneous Formulation Meets Pharmacokinetic Endpoints

Among 94 patients enrolled in the SC cohort, 68 were included in the pharmacokinetic noninferiority analysis. All 90 patients in the IV cohort were evaluable.

Both coprimary pharmacokinetic endpoints met criteria for noninferiority. The geometric mean ratio for trough concentration during cycle 3 was 1.39 (90% CI, 1.20-1.61), while the geometric mean ratio for area under the concentration-time curve from 0 to 84 days was 1.06 (90% CI, 0.92-1.21).

SC administration also resulted in slower absorption. The simulated median steady-state maximum concentration was approximately 39% lower with 45-mg SC mosunetuzumab than with 30-mg IV administration.

Responses Remain Durable With Subcutaneous Administration

All 94 patients receiving SC mosunetuzumab were included in the efficacy analysis.

The ORR was 76.6% (95% CI, 66.7%-84.7%), with 61.7% (95% CI, 51.1%-71.5%) achieving a CR. Median DOCR was 34.6 months (95% CI, 20.7 months-not evaluable), and median PFS was 23.7 months (95% CI, 14.6 months-not evaluable). Median overall survival had not been reached.

A prespecified sensitivity analysis excluding 1 patient who died or discontinued treatment before undergoing a tumor assessment produced similar findings, with an ORR of 77.4%, CR rate of 62.4%, and median PFS of 24.0 months.

Overall response, CR, duration of response, DOCR, and PFS with the SC formulation were similar to outcomes observed with IV mosunetuzumab.

Activity Observed in High-Risk Disease

Clinically meaningful responses were also observed among patients with several high-risk disease characteristics.

CR was achieved by 61.0% of patients with Ann Arbor stage III or IV disease and 59.1% of those with bulky disease greater than 7 cm. Among patients with disease progression within 24 months after starting first-line treatment, the CR rate was 56.1%.

CR rates were 50.0% among patients who were double refractory to previous therapy and 42.9% among those with elevated lactate dehydrogenase levels.

At 18 months, the PFS event-free rate was 56.8% (95% CI, 46.4%-67.2%) in the overall population and remained at least 50% across the evaluated high-risk subgroups.

Cytokine Release Syndrome Predominantly Low Grade

Almost all patients receiving SC mosunetuzumab experienced at least 1 adverse event (AE), with any-grade AEs reported in 98.9%.

The most common AEs were injection-site reactions (60.6%), fatigue (35.1%), CRS (29.8%), and diarrhea (20.2%). Grade 3 or 4 AEs occurred in 48.9% of patients, and 39.4% experienced serious AEs.

CRS was predominantly low grade, with grade 1 or 2 events occurring in 27.6% of patients and grade 3 events in 2.1%. All CRS events occurred during cycle 1 and had resolved by the data cutoff.

The median time from the most recent mosunetuzumab dose to CRS onset was 2 days, and median CRS duration was 2 days. Tocilizumab was administered to 8.5% of patients, corticosteroids to 6.4%, and both treatments to 2.1%.

Grade 5 AEs unrelated to lymphoma progression occurred in 5.3% of patients. These included COVID-19–related events and occurred in the context of nonconcurrent enrollment of the SC and IV cohorts during the COVID-19 pandemic. Investigators noted that this timing complicated direct comparisons of fatal events between formulations.

Implications for Managed Care

The availability of an SC formulation of a bispecific antibody could have implications for treatment administration and resource utilization in R/R FL.

Compared with IV treatment, SC administration may reduce some of the infrastructure and time associated with intravenous infusions, although the study did not directly evaluate health care resource utilization, costs, or patient preferences.

The similar efficacy observed between SC and IV mosunetuzumab is therefore notable as health systems and payers consider how bispecific antibodies can be incorporated into broader treatment settings.

CRS monitoring remains an important consideration. Although most CRS events with SC mosunetuzumab were low grade and confined to cycle 1, appropriate monitoring and access to supportive interventions remain necessary.

Conclusion

SC mosunetuzumab met pharmacokinetic noninferiority criteria compared with IV administration and demonstrated durable antitumor activity in patients with R/R FL, including those with high-risk disease characteristics. With an ORR of 76.6%, CR rate of 61.7%, and predominantly low-grade CRS, the findings support SC administration as a potential alternative approach to delivering mosunetuzumab while maintaining clinical efficacy.

Reference

Bartlett NL, Sehn LH, Assouline S, et al. Fixed-duration subcutaneous mosunetuzumab in relapsed/refractory follicular lymphoma: pivotal phase 2 primary analysis. Am J Hematol. 2026;101(5): 986–997. doi:10.1002/ajh.70225.