Background
Phase II, single-arm, multicenter study. 90 patients with R/R FL (grade 1–3a) after ≥2 prior lines including anti-CD20 and alkylating agent. Mosunetuzumab is a CD20×CD3 bispecific antibody given intravenously on a step-up dosing schedule with a fixed 8-cycle duration — the first fixed-duration bispecific antibody approval in lymphoma.
Interventions and follow up
Regimen: Mosunetuzumab IV with step-up dosing (1/2/60 mg cycle 1) then 60 mg cycle 2 and 30 mg cycles 3–8 every 3 weeks; extended to 17 cycles if PR/SD; in R/R follicular lymphoma after ≥2 prior lines
Primary endpoint: Complete response rate (independent review committee)
mFollow up: ~37.4 months (3-year update)
Primary endpoint: Complete response rate (independent review committee)
mFollow up: ~37.4 months (3-year update)
Results
CR rate (primary): 60.0% (95% CI 49.1–70.2%)
ORR: 77.8%
36-month OS: 82.4%
mDOR (CR patients): Not reached
mPFS: 24.0 months
ORR: 77.8%
36-month OS: 82.4%
mDOR (CR patients): Not reached
mPFS: 24.0 months
Adverse events
CRS/neurologic: CRS any grade 44.4%, grade ≥3 CRS 0%; ICANS any grade 3.3%, grade ≥3 0%; no treatment-related deaths from CRS
Hematologic/infectious: Grade ≥3 neutropenia 24.4%, grade ≥3 infections 12.2%, hypogammaglobulinemia any grade 26.7%
Hematologic/infectious: Grade ≥3 neutropenia 24.4%, grade ≥3 infections 12.2%, hypogammaglobulinemia any grade 26.7%
Conclusions
Mosunetuzumab achieved a 60% CR rate with 0% grade ≥3 CRS, durable responses (mDOR not reached in CRs), and a fixed 8-cycle treatment duration — establishing the first fixed-duration bispecific antibody option for R/R FL with a favorable outpatient-compatible profile.
Key Limitations
Single-arm Phase II with no randomized comparator. The mPFS of 24.0 months is shorter than CAR-T (ZUMA-5, TRANSCEND FL), suggesting potentially less durable disease control despite favorable safety. The relatively small sample (n=90) limits subgroup analysis. The step-up dosing requires careful monitoring during cycle 1. Cross-trial comparisons with CAR-T are confounded by differing populations.
Clinical Context
Mosunetuzumab received FDA accelerated approval (December 2022) and EMA conditional approval (June 2022) for R/R FL after ≥2 prior lines — the first bispecific antibody approved in this setting. Its fixed-duration, off-the-shelf, outpatient-compatible profile and 0% grade ≥3 CRS make it attractive for patients ineligible for or wishing to defer CAR-T. ESMO recognizes bispecific antibodies as an option in multiply relapsed FL.