Glofitamab Shows High and Durable Remissions in Heavily Pretreated Mantle Cell Lymphoma

Updated findings from a phase 1/2 trial (NCT03075696) confirm that the CD20xCD3 bispecific antibody glofitamab continues to demonstrate substantial activity in patients with heavily pretreated relapsed or refractory mantle cell lymphoma (MCL), including those with adverse prognostic features.

Dr Estefania Mulvihill (F. Hoffman-La Roche, Switzerland) presented these results on behalf of the poster first author, Dr Tycell Phillips (City of Hope, Duarte, CA, USA), at the 13th Society of Hematologic Oncology (SOHO) 2025 Annual Meeting in Houston, TX [1]. The phase 1/2  NP30179 study evaluated glofitamab monotherapy in patients with R/R B-cell lymphomas, with obinutuzumab pretreatment (Gpt) to mitigate the risk of cytokine release syndrome (CRS) with glofitamab [2]. Dr Mulvill presented the subgroup data for patients with R/R MCL.13th Society of Hematologic Oncology (SOHO) 2025 Annual Meeting [1]. The phase 1/2  NP30179 study evaluated glofitamab monotherapy in patients with R/R B-cell lymphomas, with obinutuzumab pretreatment (Gpt) to mitigate the risk of cytokine release syndrome (CRS) with glofitamab [2]. Dr Mulvihill presented the subgroup data for patients with R/R MCL.

Patients received obinutuzumab pretreatment followed by step-up glofitamab dosing: 2.5 mg on day 8 and 10 mg on day 15 of cycle 1, and then 16 to 30 mg on day 1 of cycles 2 through 12. Responses were investigator-assessed using Lugano 2014 criteria. Tumour biopsies were categorised as classical, blastic, or pleomorphic, and analysed for Ki-67 and p53. Minimal residual disease (MRD) was assessed using clonoSEQ in genomic or plasma DNA.

The intent-to-treat population (n=61) were heavily pretreated, with a median of 2 prior lines; 55% had received prior BTK inhibitor therapy, and 73% were refractory to their last regimen. Over half, 51.7%, were refractory to a BTK inhibitor.

Nevertheless, the overall response rate was 82% and the complete response rate was 77%. At data cutoff, 57.4% of complete responders remained in remission. Median progression-free survival was 18.0 months (95% CI 11.3-not estimable). Median overall survival was not estimable (95% CI 21.6-not estimable) at a median follow-up of 24.2 months.

Responses were consistent across baseline clinical subgroups, including those with high-risk features. Among 46 patients with evaluable baseline biopsies, 25 had at least 1 poor prognostic marker (blastoid morphology, Ki-67 greater than 50 percent, or p53 >50%). Complete response rates were 68% in high-risk patients compared with 81% in those without high-risk features.

Of 31 patients in complete response at the end of treatment, 17 had a trackable MRD clone. Eleven of 12 evaluable patients achieved undetectable MRD by cycle 3, suggesting early and deep molecular responses.

Dr Mulvihill concluded that the updated phase 1/2 data confirm that glofitamab induces high and durable response rates, including in heavily pretreated and biologically high-risk MCL. Glofitamab’s activity in this trial compares favorably to historical outcomes with salvage therapies in MCL, particularly after BTK inhibitor failure, a setting with limited options and typically poor prognosis. The early achievement of undetectable MRD indicates potential for long-term disease control. With more than half of complete responders still in remission at 2 years and encouraging MRD clearance, glofitamab appears poised to reshape the therapeutic landscape for relapsed or refractory MCL.

1. Mulvihill E, et al. Glofitamab Induces High Response Rates and Durable Remissions in Patients With Heavily Pretreated Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL), Including Those With a Poor Prognosis: Subgroup Results From a Phase 1/2 Trial. Abstract MCL-553, SOHO 2025, 2-7 Sept.
2. Phillips TJ, et al J Clin Oncol. 2025 Jan 20;43(3):318-328.

Medical writing support was provided by Dr Rachel Giles.
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Posted on 19 September 202519 September 2025