Glofitamab Shows Durable Responses in R/R MCL After 3.5 Years of Follow-Up

Updated data from a phase 1/2 trial of fixed-duration glofitamab (Columvi; Genentech) in relapsed/refractory (R/R) mantle cell lymphoma (MCL) show the bispecific T-cell engager sustained efficacy and a manageable safety profile after a median follow-up of more than 41 months, including in patients previously treated with a Bruton tyrosine kinase (BTK) inhibitor.

The findings were presented in an oral session at the 2026 American Society of Clinical Oncology annual meeting by Yasmin H. Karimi, MD, clinical assistant professor of medicine in the Division of Hematology/Oncology, University of Michigan.¹

Background and Rationale

Despite recent advances, R/R MCL remains a difficult-to-treat disease, with limited durability of response for patients beyond chimeric antigen receptor (CAR) T-cell therapy. This has created a growing unmet need for effective options for patients who progress following treatment with BTK inhibitors, as covalent BTK inhibitor use continues to expand into the first-line setting. Glofitamab is an off-the-shelf, fixed-duration CD20 x CD3 bispecific with a 2:1 format—with a pair of CD20-binding arms and a single CD3 arm—designed to redirect T cells against malignant B cells. It is already approved in the United States for patients who have received at least 2 therapies for diffuse large B-cell lymphoma (DLBCL).²

Patient Population and Study Design

Sixty-one patients with R/R MCL after at least 1 prior line of systemic therapy were enrolled in the phase 1/2 trial (NCT03075696); 60 were treated. This heavily pretreated population had a median of 2 prior lines of therapy (range 1–5) and a median age of 72 years. The majority had advanced-stage disease (Ann Arbor stage III/IV: 86.9%), and the cohort was characterized by multiple high-risk features: 62.3% of the patients had a Ki-67 proliferation index ≥ 30%, while a TP53 mutation was seen in 19.7%, and blastoid or pleomorphic morphology was reported in 9.8%. In addition, 73.8% of the patients were refractory to their last prior therapy. More than half (55.7%, n = 34) had received a BTK inhibitor.¹

Patients received obinutuzumab pretreatment (either 1000 mg or 2000 mg) on Cycle 1, Day 1, followed by glofitamab step-up dosing on Days 8 and 15 of Cycle 1, then target dosing of 16 mg or 30 mg every 3 weeks for up to 12 cycles.

Efficacy Results Show High ORR

Across the entire study population, the overall response rate (ORR) was 82% and the complete response (CR) rate was 77%. With a data cutoff of September 8, 2025, and a median follow-up of 41.5 months, nearly half of all patients (48.9%) had ongoing CRs. The estimated 33-month duration of CR (DOCR) rate was 50.5%, and the median DOCR was 40.8 months. Median progression-free survival (PFS) was 18.0 months, and median overall survival (OS) had not yet been reached.

Among those previously treated with BTK inhibitors, the ORR was 73.5% and the CR rate was 70.6%, with a median DOCR of 15.4 months and median OS of 29.9 months, which investigators characterized as meaningful outcomes in a population historically associated with poor prognosis after failure on BTK inhibitors. Notably, sensitivity analyses censoring for COVID-19–related deaths extended the median DOCR in the group with prior BTK inhibitor treatment to 40.8 months, Karimi noted in her slides, suggesting a true treatment benefit may be underestimated in this dataset given the timing of the pandemic. Among patients achieving a CR at the end of treatment, 65.6% remained progression-free and alive 2 years after completing therapy, she added in the presentation.

A landmark analysis of minimal residual disease (MRD) status in CR patients further reinforced the depth and durability of responses: patients with undetectable MRD at Cycle 3 and at the end of treatment had substantially superior PFS compared to those with detectable MRD, with hazard ratios of 0.30 and 0.03, respectively.

Higher Obinutuzumab Dose Linked to Lower CRS Rates

No new safety signals emerged with extended follow-up. Cytokine release syndrome (CRS) remained the most common adverse event, occurring in 70% of patients (grade 1-2, 58.3%; grade 3-4, 11.6%). CRS rates were notably lower among patients pretreated with 2000 mg of obinutuzumab (63.6%) versus the 1000 mg cohort (87.5%). Infections, including COVID-19, were observed during treatment; 3 patients died due to COVID-19–related causes. B-cell recovery was observed 12-18 months after the end of treatment.

The investigators concluded that fixed-duration glofitamab monotherapy offers robust and durable efficacy in heavily pretreated patients with R/R MCL, including those who have progressed on BTK inhibitors. The drug's off-the-shelf availability and fixed-duration administration are cited as practical advantages for patients requiring rapid disease control. Glofitamab is now being evaluated in the ongoing phase 3 GLOBRYTE trial,³ which will further define its role in this setting outside of the COVID-19 era.

References

1. Karimi Y, Hutchings M, Phillips TJ, et al. 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. J Clin Oncol. 2026;44 (suppl 16): abstr 7006. doi:10.1200/JCO.2026.44.16_suppl.7006
2. FDA grants accelerated approval to glofitamab-gxbm for selected relapsed or refractory large B-cell lymphomas. FDA newsroom. June 16, 2023. Accessed June 12, 2026. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-glofitamab-gxbm-selected-relapsed-or-refractory-large-b-cell
3. Phillips TJ, Matasar M, Eyre TA, et al. GLOBRYTE: A phase 3, open-label, multicenter, randomized trial evaluating glofitamab monotherapy in patients with relapsed or refractory mantle cell lymphoma. Blood. 2023;142 (suppl 1): asbtr 3052. doi:10.1182/blood-2023-173946