Subcutaneous Mosunetuzumab-Polatuzumab May Widen Access in R/R LBCL

A subcutaneous injection that takes minutes, instead of an hours-long infusion chair appointment, could reshape where clinicians deliver a bispecific antibody combination for relapsed or refractory large B-cell lymphoma (LBCL), a form of non-Hodgkin lymphoma. That shift in site of care is the focus of a randomized phase 2 trial published in the American Journal of Hematology.¹

Chair Time Shapes Access to Bispecific Therapy

Bispecific antibodies that redirect T cells against CD20-expressing B cells have reshaped treatment for relapsed/refractory (R/R) LBCL, offering an off-the-shelf alternative to chimeric antigen receptor (CAR) T-cell therapy. Most are given intravenously (IV), a route that requires a dedicated infusion chair and enough time to limit the visit mainly to larger centers. A subcutaneous (SC) formulation changes that math. In an 8-country time-and-motion study, mean chair time for rituximab, another CD20-targeted antibody used in LBCL, was 262.1 minutes for IV infusion vs 67.3 minutes for SC injection, a roughly 74% reduction.²

The same logic underlies interest in SC mosunetuzumab, a CD20×CD3 bispecific antibody: a shorter visit could move bispecific therapy into community practices. The 8-nation study differed from the phase 3 SUNMO trial (NCT05171647), which tested the same SC mosunetuzumab-polatuzumab vedotin combination against a chemotherapy-containing regimen. This phase 2 trial instead compared it with a nonchemotherapy, rituximab-based regimen, isolating mosunetuzumab's own contribution.¹

The analysis drew from the randomized phase 2 cohort of an ongoing, open-label, multicenter phase Ib/II trial (NCT03671018). Investigators enrolled 80 adults with R/R LBCL, including diffuse large B-cell lymphoma, grade 3b follicular lymphoma, high-grade B-cell lymphoma, or transformed follicular lymphoma, with at least 1 prior line of anti-CD20-containing therapy. Patients were randomized 1:1 to subcutaneous mosunetuzumab plus polatuzumab vedotin (Mosun-Pola; n = 40) or rituximab plus polatuzumab vedotin (R-Pola; n = 40).

Mosunetuzumab was given subcutaneously with step-up dosing in cycle 1 (5 mg, then 45 mg twice), then 45 mg on day 1 of cycles 2 through 8, with no hospitalization required. Polatuzumab vedotin, an antibody-drug conjugate, was given IV at 1.8 mg/kg on day 1 of cycles 1 through 6 in both arms; the R-Pola arm added IV rituximab (375 mg/m²) on day 1 of cycles 1 through 8. The primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR).

Response Rates and Survival Favored the Subcutaneous Combination

With more than 2 years of follow-up, IRC-assessed best ORR was 77.5% (95% CI, 61.6%-89.2%) with Mosun-Pola vs 50.0% (95% CI, 33.8%-66.2%) with R-Pola, and complete response rates were 55.0% vs 35.0%. Median progression-free survival was 25.4 months with Mosun-Pola vs 6.4 months with R-Pola (HR, 0.47); median overall survival was not reached with Mosun-Pola vs 25.5 months with R-Pola (HR, 0.78).

Subgroup findings should be read cautiously given the trial's size, the researchers noted. Twenty patients who crossed from R-Pola to Mosun-Pola after an inadequate response achieved a 50.0% response rate, suggesting the bispecific antibody retained activity after rituximab-based treatment failed.

Any-grade adverse events occurred in all patients in both arms; grade 3 or higher events occurred in 60.0% of the Mosun-Pola arm vs 53.8% of the R-Pola arm. Injection-site reactions, unique to the subcutaneous route, affected 57.5% of patients receiving Mosun-Pola (grade 1, 37.5%; grade 2, 20.0%) and did not occur with R-Pola. Cytokine release syndrome (CRS) occurred in 12.5% of Mosun-Pola patients, all grade 1 or 2, with a median onset and duration of 2 days each; 1 event led to hospitalization, and no grade 3 or higher CRS or neurotoxicity occurred in either arm.

“Overall, subcutaneous administration of mosunetuzumab and outpatient use of this regimen, with the lowest CRS rate among all T-cell-based regimens, favor Mosun-Pola for community adoption,” the researchers wrote.

Limitations Reflect the Trial's Early-Phase, Small-Cohort Design

The researchers cited the small sample size and crossover design as limitations, noting the crossover may have blunted the observed survival benefit. A single-agent polatuzumab vedotin arm would have offered a cleaner read on mosunetuzumab's own contribution, they acknowledged, though they considered R-Pola the more relevant control. The subcutaneous route was not compared head-to-head against IV mosunetuzumab.

The parent trial is listed as active but not recruiting. These results represent 1 phase 2 cohort, not a phase 3 analysis, which is yet to come.

References

1. Chavez JC, Bastos-Oreiro M, Diefenbach C, et al. A randomized phase II study of subcutaneous mosunetuzumab in combination with polatuzumab vedotin compared with rituximab plus polatuzumab vedotin in patients with relapsed or refractory large B-cell lymphoma. Am J Hematol. 2026;101(9):2177-2189. doi:10.1002/ajh.70403
2. De Cock E, Kritikou P, Sandoval M, Tao S, Wiesner C, Carella AM, Ngoh C, Waterboer T. Time savings with rituximab subcutaneous injection versus rituximab intravenous infusion: a time and motion study in eight countries. PLoS One. 2016;11(6):e0157957. doi:10.1371/journal.pone.0157957