Glofitamab Monotherapy Demonstrates Durable Responses in Relapsed/Refractory Mantle Cell Lymphoma

Relapsed/refractory mantle cell lymphoma (R/R MCL) carries a poor prognosis, particularly in patients with high-risk disease features or those who have progressed after Bruton tyrosine kinase inhibitor (BTKi) therapy.

Glofitamab, a CD20 x CD3 2:1 bispecific antibody engineered to redirect T cells against malignant B cells, has emerged as a promising fixed-duration treatment option in this setting. Updated long-term data from a phase 1/2 trial (NCT03075696) now provide the most mature efficacy and safety readout to date for this agent in R/R MCL.

The data were presented at the 2026 American Society of Clinical Oncology Annual Meeting in Chicago.

MCL and Glofitamab

MCL is a rare, aggressive form of non-Hodgkin lymphoma (NHL) that begins in the mantle zone, the outer area of small lymphocytes surrounding a lymphatic nodule. In some cases, MCL cells can enter the lymphatic channels and blood to spread to other lymph nodes or tissues. MCL is often diagnosed at an advanced stage and is incurable. However, prompt diagnosis and treatment can reduce disease progression and may result in complete remission for years.¹

Of all NHL cases, MCL accounts for approximately 5% in the United States and Europe, with an estimated incidence of 4 to 8 individuals per million, per year.¹

Glofitamab represents a novel approach for the treatment of patients with MCL. Rather than targeting a single antigen, glofitamab simultaneously engages 2 targets: CD20 on malignant B cells and CD3 on T cells. What distinguishes it from other bispecific antibodies is its 2:1 binding configuration—a structural design that enhances tumor cell engagement and directs T cells to seek out and destroy malignant B cells.²

Already approved in more than 30 countries for R/R diffuse large B-cell lymphoma following at least 2 prior lines of therapy, glofitamab is being evaluated as a treatment option for patients with MCL.²

Investigating Glofitamab

Patients with R/R MCL who had received at least 1 prior line of systemic therapy were enrolled in the trial. All patients received obinutuzumab pretreatment (Gpt) on cycle 1, day 1, as either a single 1000-mg dose (n = 17) or a split 2000-mg dose over 2 days (n = 44). Glofitamab was then introduced via step-up dosing: 2.5 mg on cycle 1, day 8, followed by 10 mg on cycle 1, day 15, and then the target dose of 16 or 30 mg every 3 weeks from cycles 2 through 12. Key efficacy end points included complete response (CR) rate, overall response rate (ORR), duration of CR (DoCR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS).³

A total of 61 patients were enrolled, and 60 were treated. The population was heavily pretreated, with a median of 2 prior lines of therapy (range, 1-5) and a median age of 72 years. The majority had advanced disease, with 86.9% presenting with Ann Arbor stage III or IV. High-risk features were common: 62.3% of patients had a Ki-67 proliferation index of 30% or greater, 9.8% had blastoid or pleomorphic variants, and 19.7% carried TP53 mutations. More than half of patients (55.7%) had received prior BTKi therapy.³

Glofitamab Yields Favorable Response Rates

As of the September 8, 2025, data cutoff, with a median OS follow-up of 41.5 months, glofitamab demonstrated an ORR of 82% and a CR rate of 77%. The median DoCR reached 40.8 months, with nearly half of patients (48.9%) maintaining ongoing CRs at the data cutoff. The estimated 33-month DoCR and DoR rates were 50.5% and 47.4%, respectively. The median PFS was 18 months and the median OS had not yet been reached.³

In the BTKi-exposed subgroup, responses remained meaningful: 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—a noteworthy outcome in a population with historically limited options following BTKi failure.³

Glofitamab Safety Profile Is Consistent With Existing Evidence

No new safety signals emerged with longer follow-up. Cytokine release syndrome (CRS) remained the most frequently observed adverse event, occurring in 70% of patients, with most cases being grade 1 to 2 (58.3%). Importantly, CRS rates were lower in the 2000-mg Gpt cohort (63.6%) than in the 1000-mg cohort (87.5%), suggesting a potential tolerability advantage of the split-dose pretreatment approach.³

Future of MCL Treatment

With nearly 3.5 years of follow-up, glofitamab monotherapy continues to demonstrate robust and durable responses in heavily pretreated R/R MCL, including in patients previously exposed to BTKi therapy. Its fixed-duration administration, manageable safety profile, and activity in high-risk disease make it a compelling option for patients in need of rapid disease control.

REFERENCES

1. Relapsed/refractory mantle cell lymphoma. Association of Cancer Care Centers. Accessed May 29, 2026. https://www.accc-cancer.org/education-and-resources/cancer-types/hematologic-malignancies/mcl

2. Phillips TJ, Carlo-Stella C, Morschhasuer F, et al. Glofitamab in relapsed/refractory mantle cell lymphoma: results from a phase I/II study. J Clin Oncol. 2025;43(3):318-328. doi:10.1200/JCO.23.02470

3. Yasmini K, 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. Presented at: 2026 American Society of Clinical Oncology Annual Meeting; May 29-June 2, 2026; Chicago, IL. Abstract 7006.