Fixed-duration glofitamab monotherapy in relapsed/refractory (R/R) mantle cell lymphoma (MCL) with/without prior Bruton's tyrosine kinase inhibitor (BTKi) exposure: Updated data after a 3.5-year follow-up.

7006 Background: Patients (pts) with advanced R/R MCL have poor outcomes, especially pts with high-risk features or those progressing after BTKi therapies. Glofitamab is a CD20xCD3 2:1 bispecific antibody that redirects T cells to eliminate malignant B cells. A Phase 1/2 trial (NCT03075696) evaluated glofitamab monotherapy, given with step-up dosing (SUD) after obinutuzumab pretreatment (Gpt), in pts with R/R MCL. Prior analyses showed high response rates and manageable safety, regardless of prior BTKi exposure (Phillips, et al. ASCO 2024). We report longer follow-up data from this MCL cohort. Methods: Pts with R/R MCL after ≥1 prior line of systemic therapy received Gpt (single 1000 mg dose or 2000 mg split over 2 days, as needed) on cycle (C)1 day (D)1. Glofitamab SUD was given on C1D8 (2.5 mg) and C1D15 (10 mg), then the target dose of 16 or 30 mg every 3 weeks on D1 of C2–12. Efficacy endpoints included investigator-assessed complete response (CR) rate, overall response rate (ORR), duration of CR (DoCR), duration of response (DoR), progression free survival (PFS), and overall survival (OS). Results: As of Sept 8, 2025, 61 pts with R/R MCL were enrolled (Gpt: 1000 mg, n=17; 2000 mg, n=44); 60 pts were treated. The median number of prior lines of therapy was 2 (range 1–5), median age was 72.0 years (range 41–86), 86.9% of pts had Ann Arbor stage III/IV, and 26.3% had a simplified MCL International Prognostic Index score of ≥6. Pts had high-risk disease features such as Ki-67 proliferation index ≥30% (62.3%), blastoid/pleomorphic variants (9.8%), and TP53 mutation (19.7%). The median number of glofitamab cycles received was 12 (range 1–13). With a median OS follow-up of 41.5 months (mo; 95% CI: 37.4–48.7), the ORR and CR rate were 82% and 77%, respectively. Median DoCR was 40.8 mo (95% CI: 14.1–NE); 48.9% of pts had ongoing CRs at the data cut-off. Estimated 33-mo DoCR and DoR rates were 50.5% and 47.4%, respectively. Median (95% CI) PFS was 18 mo (11.3–42.8) and OS was NE (26.9–NE). For pts who received prior BTKi therapy (n=34 [55.7%]), the ORR and CR rate were 73.5% and 70.6%, respectively. Median (95% CI) DoCR was 15.4 mo (8.3–NE), PFS was 11.3 mo (5.1–32.6), and OS was 29.9 mo (11.3–NE). Estimated 33-mo DoCR and DoR rates were 42.7% and 41.0%, respectively. No new safety signals were observed. Cytokine release syndrome remained the most common adverse event (n=42/60, 70%; Grade 1–2, 58.3%; Grade 3–4, 11.6%), with lower rates in the 2000 mg (n=28/44, 63.6%) vs 1000 mg (n=14/16, 87.5%) Gpt cohorts. Conclusions: Updated data on fixed-duration glofitamab monotherapy in heavily pretreated pts with R/R MCL show robust efficacy and manageable safety, including in BTKi-exposed pts. Glofitamab monotherapy is a suitable treatment for pts with R/R MCL in need of rapid disease control and is under investigation in the Phase 3 GLOBRYTE trial. Clinical trial information: NCT03075696 .