Fixed treatment duration mosunetuzumab continues to demonstrate clinically meaningful outcomes in patients with relapsed/refractory (R/R) follicular lymphoma (FL) after ≥2 prior therapies: 5-year follow-up of a pivotal Phase II study

Abstract Background: Mosunetuzumab is the first FDA- and EMA-approved CD20xCD3 T-cell engaging bispecific antibody for the treatment of R/R FL after ≥2 prior lines of therapy. In a pivotal Phase II study (NCT02500407), fixed-duration mosunetuzumab demonstrated high response rates, durable remissions, and a manageable safety profile in patients with R/R FL (Budde et al. Lancet Oncol 2022; Shadman et al. ASH 2024; Cheah et al. EHA 2025). We report updated efficacy and safety data for mosunetuzumab in patients with R/R FL after a median follow-up of 5 years. Methods: Eligible patients with R/R FL Grade 1–3a and ≥2 prior therapies received intravenous mosunetuzumab for a fixed duration with step-up dosing in Cycle (C)1. Hospitalization was not mandatory. Patients with a complete response (CR) by C8 completed therapy with no additional cycles; patients with partial response or stable disease post C8 could continue treatment for up to 9 additional cycles (a total of 17 cycles). Efficacy analyses by investigator assessment (Cheson et al. 2007 criteria) included CR rate, overall response rate (ORR), duration of response (DOR), duration of CR (DOCR), progression-free survival (PFS), overall survival (OS) and time to next treatment (TTNT). Safety and tolerability were assessed by describing the incidence and severity of adverse events (AEs). After the AE reporting period (90 days after the last dose or start of new anti-lymphoma treatment), mosunetuzumab-related serious AEs were to be reported. Results: Ninety patients with R/R FL were enrolled, of whom 52% had a history of disease progression within 24 months from the start of first-line therapy (POD24) and 53% were double refractory. Median age was 60 years (range: 29–90) and median prior lines of therapy was 3 (range: 2–10). As of May 1, 2025, median time on study was 60.2 months (range: 2–72). In the overall population (N=90), the ORR and CR rate were 78% and 60%, respectively; median DOR (n=70) was 46.4 months (95% confidence interval CI: 18.7–not estimable NE), and median DOCR (n=54) was not reached (95% CI: 44.1–NE). The 54-month DOR and DOCR rates were 46% (95% CI: 33.8–59.1) and 52% (95% CI: 36.2–67.9), respectively. Median PFS was 24.0 months (95% CI: 12.0–53.2) in all patients, and 61.0 months (95% CI: 47.6–NE) in patients who achieved CR. The 5-year PFS rates were 36% (95% CI: 25.3–47.7) and 57% (95% CI: 42.0–71.6) in all patients and patients with CR, respectively. Median OS was not reached (95% CI: NE), and the 5-year OS rate was 78% (95% CI: 69.6–87.4). Eighteen deaths were reported; 13 due to progressive disease, 1 each due to unexplained death, cardiac arrest and sepsis, and 2 with unknown cause. The median TTNT in all patients was 64.1 months (95% CI: 21.7–NE), and the 5-year TTNT rate was 51% (95% CI: 39.8–61.8). Five patients received mosunetuzumab retreatment of whom 3 achieved a subsequent CR. In the 47 patients with POD24, the ORR (81%) and CR rate (60%) were consistent with those observed in the overall population. Median DOCR was 50.1 months (95% CI: 18.7–NE), and the 54-month DOCR rate was 48% (95% CI: 24.9–71.5); median PFS was 21.7 months (95% CI: 11.6–61.0) and the 5-year PFS rate was 36.9% (95% CI: 20.7–53.1), with a small number of patients remaining at risk. No new AEs were reported since the 4-year follow-up. All patients had at least one AE; the most common AE was cytokine release syndrome (CRS; 44%). CRS events were mainly Grade 1/2 (Grade 1, n=23; Grade 2, n=15; Grade 3, n=1; Grade 4, n=1) and were all resolved. AEs leading to treatment discontinuation occurred in 4% of patients; no treatment-related Grade 5 AEs occurred. The recovery of B cells and immunoglobulin M (IgM) was observed in patients with a CR. Conclusions: This report represents the longest follow-up for a CD20xCD3 bispecific antibody in R/R FL. Fixed-duration mosunetuzumab treatment yields durable responses, and long-term survival continues to be observed in patients with heavily pre-treated R/R FL. The data highlight the durable long-term remissions achieved with mosunetuzumab in this setting. Updated data confirm that B-cell recovery is observed and sustained. In parallel, IgM levels recover with a similar time course. In both cases after 2 years a majority of patients have recovered to normal levels. The safety profile remained manageable, with no new toxicities reported.