Fixed-Duration Mosun-Pola Yields High ORR in R/R Mantle Cell Lymphoma

Fixed-duration mosunetuzumab (Lunsumio) combined with polatuzumab vedotin (Polivy), also known as Mosun-Pola, produced durable responses in patients with relapsed or refractory mantle cell lymphoma (MCL) who had progressed after treatment with a Bruton tyrosine kinase (BTK) inhibitor, according to results from a multicenter phase 2 study (NCT03671018) published in Blood.¹

Among 42 evaluable patients, the objective response rate (ORR) was 88.1% (95% CI, 74.4%-96.0%), and the complete response (CR) rate was 78.6% (95% CI, 63.2%-89.7%) At a median follow-up of 15.9 months, median progression-free survival (PFS) was 18.6 months (95% CI, 13.9-not estimable). Efficacy remained consistent across high-risk subgroups.

Safety and Outpatient Feasibility

Regarding safety, CRS occurred in 42.9% of patients and was limited to grade 1/2 events. Of note, hospitalization to monitor for CRS was not required under the protocol, a feature the authors identified as relevant to the regimen's outpatient feasibility.

The investigational regimen combines a CD20xCD3 bispecific antibody with a CD79b-directed antibody-drug conjugate, pairing 2 independent mechanisms of B-cell killing in a fixed-duration, outpatient schedule. In a disease where chimeric antigen receptor T-cell (CAR T) therapies have demonstrated high response rates with durable remissions, logistical challenges can preclude their use in practice, positioning Mosun-Pola as a potentially accessible outpatient alternative for those with relapsed/refractory disease.

“By also offering meaningful safety and logistical advantages, Mosun-Pola represents an accessible and practical outpatient-based therapy, and is a potentially important therapeutic option for patients with relapsed/refractory MCL,” authors Budde et al wrote in the publication. “Further study is warranted, including how to optimally sequence among newer therapies for MCL.”

Phase 2 Trial Design and Patient Characteristics

The trial enrolled patients with MCL who had received at least 2 prior lines of therapy, including a BTK inhibitor.² The population reflected a heavily pretreated, high-risk cohort: median age was 68 years (range, 44-82), the median number of prior therapies was 3, and 26% of patients had previously received CAR T-cell therapy. Ann Arbor stage 3/4 disease was present in 91% of patients, and 48% had a simplified MCL International Prognostic Index score of 6 or higher. High-risk disease features were common, including Ki-67 expression of 50% or greater in 67% of patients, blastoid or pleomorphic morphology in 38%, and TP53 aberration in 48%.

The regimen consisted of mosunetuzumab administered subcutaneously in an outpatient setting for 17 cycles. Cycle 1 used step-up dosing, with 5 mg on day 1, followed by 45 mg on days 8 and 15, an approach intended to mitigate CRS; subsequent cycles used a fixed 45-mg dose on day 1 every 3 weeks. Polatuzumab vedotin was given intravenously at 1.8 mg/kg on day 1 of cycles 1 through 6.

The primary end point was centrally assessed best ORR; secondary end points included duration of response, PFS, event-free survival, overall survival, and safety.

REFERENCES

1. Budde LE, Kamdar M, Assouline SE, et al. Mosunetuzumab plus polatuzumab vedotin for relapsed/refractory MCL after BTK inhibitor therapy: a phase 2 study. Blood. 2026;148(6):682-692. doi:10.1182/blood.2025032422

2. A Study to Evaluate the Safety and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With Polatuzumab Vedotin in B-Cell Non-Hodgkin Lymphoma. ClinicalTrials.gov. Updated November 29, 2024. Accessed August 26, 2026. https://clinicaltrials.gov/study/NCT03671018