The European Commission has approved glofitamab (; Genentech/Roche) in combination with gemcitabine and oxaliplatin (GemOx) for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) not otherwise specified who are ineligible for autologous stem cell transplant (ASCT).*
An Aggressive disease
DLBCL is an aggressive type of non-Hodgkin lymphoma (NHL) and is one of the most prevalent types of blood cancer among adults, accounting for about one in three cases of NHL. [1] Approximately 160,000 people worldwide are diagnosed with DLBCL each year. In Europe, an estimated 38,000 people are diagnosed with DLBCL each year. [1][2][3]
While the disease is generally responsive to treatment in the frontline, approximately four out of ten DLBCL patients (40%) will relapse after first-line treatment, at which time required salvage therapy options are limited, resulting in overall poor outcome and relatively short survival.[4][5]
Although second-line treatment advances have been made, challenges with the accessibility of existing medicines and the aggressive nature of DLBCL underscores the urgent need for immediately available treatment options that can control the disease and improve survival.[6]
Glofitamab in combination with GemOx offers an ‘off-the-shelf’ treatment regimen, readily available for infusion in any setting, meaning patients can avoid delays in starting their next treatment. Glofitamab is also designed to be given for a fixed period offering a target end date for people’s course of therapy and the possibility of a treatment-free period after completion.
Targeting CD3
Glofitamab is a CD20xCD3 T-cell engaging bispecific antibody designed to target CD3 on the surface of T cells and CD20 on the surface of B cells. Glofitamab was designed with a novel 2:1 structural format. This T-cell engaging bispecific antibody is engineered to have one region that binds to CD3, a protein on T cells, a type of immune cell, and two regions that bind to CD20, a protein on B cells, which can be healthy or malignant.
This dual-targeting brings the T cell in close proximity to the B cell, activating the release of cancer cell-killing proteins from the T cell.
Meeting unmet needs
With this approval, this glofitamab combination is the first bispecific antibody regimen available for people with DLBCL in Europe whose cancer has returned or for those who did not respond to initial treatment.
In July 2023, glofitamab received a conditional marketing authorization to treat people with R/R DLBCL after two or more lines of systemic therapy. In addition to today’s approval, a condition to convert the existing marketing authorization to a regular approval has been fulfilled.
“Glofitamab is the first treatment of its kind to improve survival outcomes for people with DLBCL whose cancer has returned after first-line therapy,” noted Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development.
“With this approval, glofitamab can now benefit patients even earlier in their treatment, adding to its existing value as an important treatment for DLBCL,” Garraway further noted.
“People with R/R DLBCL not eligible for ASCT represent a challenging population, especially those with primary refractory disease or early relapse whose need for a readily accessible and effective therapy is insufficiently addressed globally,” explained Franck Morschhauser, MD, PhD, Professor of Haematology, University Hospital Lille and STARGLO study investigator.
“This new glofitamab combination is immediately available if a patient’s cancer returns or doesn’t respond to first-line therapy, which is a welcome addition to manage DLBCL,” Morschhauser added.
STARGLO study
Approval is based on results from the pivotal phase 3 STARGLO study (GO41944; NCT04408638) , where glofitamab in combination with GemOx demonstrated a statistically significant and clinically meaningful overall survival (OS) improvement versus rituximab (Rituxan®/MabThera®; Genentech/Roche) and GemOx (R-GemOx) in people with R/R DLBCL.1,2 In the primary analysis (conducted after a median follow-up of 11.3 months), there was a 41% reduction in the risk of death in patients treated with glofitamab plus GemOx versus R-GemOx (hazard ratio [HR]=0.59, 95% CI: 0.40-0.89, p=0.011).
The glofitamab combination also met its key secondary endpoints, with a 63% reduction in risk of disease worsening or death (progression-free survival, PFS) compared to R-GemOx (HR=0.37; 95% CI: 0.25–0.55, p<0.0001).1,2 Follow-up analyses were conducted after all patients had completed therapy (median follow-up of 20.7 months), showing a 25.5 month median OS for people treated with the glofitamab combination, nearly double what was seen for people treated with R-GemOx at 12.9 months (HR=0.62, 95% CI: 0.43-0.88).[7][8]
Additionally, more than twice as many patients experienced a complete response (58.5% versus 25.3% respectively, with a difference of 33.2% [95% CI: 20.9-45.5]). ]7][8] Safety of the combination was consistent with the known safety profiles of the individual medicines.[7][8]
Bispecific antibody program
Glofitamab, along with mosunetuzumab (Lunsumio®; Genetech/Roche), is part of Roche’s industry-leading CD20xCD3 bispecific antibody program. Together with the clinical development of off-the-shelf allogeneic CAR T-therapies, Roche aims to provide tailored treatment options that suit the diverse needs, preferences, and experiences of people with blood cancers and healthcare systems.
Glofitamab is also being investigated in combination with Polivy® (polatuzumab vedotin) and MabThera®/Rituxan® (rituximab), cyclophosphamide, doxorubicin and prednisone (R-CHP) in previously untreated DLBCL in the phase III SKYGLO study [GO44145; NCT06047080].
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Note:* On June 15, 2023, the US Food and Drug Administration (FDA) granted accelerated approval to glofitamab-gxbm (Columvi, Genentech/Roche) for relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after two or more lines of systemic therapy.
Clinical trials
A Phase III Study Evaluating Glofitamab in Combination With Gemcitabine + Oxaliplatin vs Rituximab in Combination With Gemcitabine + Oxaliplatin in Participants With Relapsed/Refractory Diffuse Large B-Cell Lymphoma – ClinicalTrials.gov ID NCT04408638
An Open-Label Study Comparing Glofitamab and Polatuzumab Vedotin + Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone Versus Pola-R-CHP in Previously Untreated Patients With Large B-Cell Lymphoma – ClinicalTrials.gov ID NCT06047080
Highlights of Prescribing Information
Glofitamab (Columvi®; Genentech/Roche)[Prescribing Information]
Rituximab (Rituxan®/MabThera® Gentech Roche and Biogen)[Prescribing Information]
Mosunetuzumab (Lunsumio®; Genetech/Roche)[Prescribing Information]
Gemcitabine (Gemzar®; Lilly & Co) [Prescribing Information]
Oxaliplatin (Eloxatin®; Sanofi) [Prescribing Information]
References
[1] UpToDate. Patient education: Diffuse large B cell lymphoma in adults (Beyond the Basics). [Internet; cited 2025 April]. Online.
[2] World Health Organization. Numbers derived from GLOBOCAN 2022. Europe Factsheet [Internet; cited 2025 April]. Online
[3 World Health Organization. Numbers derived from GLOBOCAN 2022. Non-Hodgkin Lymphoma Factsheet [Internet; cited 2025 April]. Online.
[4] Maurer MJ, Ghesquières H, Jais JP, Witzig TE, Haioun C, Thompson CA, Delarue R, Micallef IN, Peyrade F, Macon WR, Jo Molina T, Ketterer N, Syrbu SI, Fitoussi O, Kurtin PJ, Allmer C, Nicolas-Virelizier E, Slager SL, Habermann TM, Link BK, Salles G, Tilly H, Cerhan JR. Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy. J Clin Oncol. 2014 Apr 1;32(10):1066-73. doi: 10.1200/JCO.2013.51.5866. Epub 2014 Feb 18. PMID: 24550425; PMCID: PMC3965261.
[5] Sehn LH, Salles G. Diffuse Large B-Cell Lymphoma. N Engl J Med. 2021 Mar 4;384(9):842-858. doi: 10.1056/NEJMra2027612. PMID: 33657296; PMCID: PMC8377611.
[6] Fabbri N, Mussetti A, Sureda A. Second-line treatment of diffuse large B-cell lymphoma: Evolution of options. Semin Hematol. 2023 Nov;60(5):305-312. doi: 10.1053/j.seminhematol.2023.12.001. Epub 2023 Dec 14. PMID: 38342663.
[7] Abramson J, et al. Glofitamab plus Gemcitabine and Oxaliplatin (Glofit-GemOx) for Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL): Results of a Global Randomized Phase III trial (STARGLO). Presented at: EHA Hybrid Congress; 2024 Jun 3-16. Abstract #LB3438.
[8] Abramson JS, Ku M, Hertzberg M, Huang HQ, Fox CP, Zhang H, Yoon DH, Kim WS, Abdulhaq H, Townsend W, Herbaux C, Zaucha JM, Zhang QY, Chang H, Liu Y, Cheah CY, Ghesquieres H, Simko S, Orellana-Noia V, Ta R, Relf J, Dixon M, Kallemeijn M, Mulvihill E, Huang H, Lundberg L, Gregory GP. Glofitamab plus gemcitabine and oxaliplatin (GemOx) versus rituximab-GemOx for relapsed or refractory diffuse large B-cell lymphoma (STARGLO): a global phase 3, randomised, open-label trial. Lancet. 2024 Nov 16;404(10466):1940-1954. doi: 10.1016/S0140-6736(24)01774-4. PMID: 39550172.
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