Practical Management of Aggressive B-Cell Lymphomas with CD20×CD3 Bispecific Antibodies
DOI:
https://doi.org/10.58931/cht.2025.4378Abstract
CD20×CD3 bispecific antibodies (BsAbs) have transformed the therapeutic landscape of relapsed or refractory large B-cell lymphoma (LBCL). By redirecting T cells to target CD20-expressing lymphoma cells, these off-the-shelf agents offer high response rates and durable remissions in patients who previously had limited options, including those who relapse after chimeric antigen receptor T-cell therapy. In Canada, epcoritamab and glofitamab are now approved for patients with LBCL after at least two prior lines of treatment. The combination of glofitamab, gemcitabine, and oxaliplatin has been recently approved for patients with relapsed/refractory diffuse large B-cell lymphoma not otherwise specified LBCL after at least 1 line of therapy and who are ineligible for autologous hematopoietic stem cell transplant. This review provides a practical framework for Canadian hematologists: identifying eligible patients, implementing pretreatment evaluation, safely delivering therapy in inpatient and outpatient settings, and managing toxicities such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. We will also discuss infection prophylaxis, sequencing with cellular therapies, and future directions for BsAbs in earlier treatment lines.
References
Abramson JS, Solomon SR, Arnason J, Johnston PB, Glass B, Bachanova V, et al. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of the phase 3 TRANSFORM study. Blood. 2023;141(14):1675-84. DOI: https://doi.org/10.1182/blood.2022018730
Locke FL, Miklos DB, Jacobson CA, Perales MA, Kersten MJ, Oluwole OO, et al. Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma. N Engl J Med. 2021.
Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin’s lymphoma. N Engl J Med. 1995;333(23):1540-5. DOI: https://doi.org/10.1056/NEJM199512073332305
Neelapu SS, Jacobson CA, Ghobadi A, Miklos DB, Lekakis LJ, Oluwole OO, et al. Five-year follow-up of ZUMA-1 supports the curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma. Blood. 2023;141(19):2307-15. DOI: https://doi.org/10.1182/blood.2022018893
Abramson JS, Palomba ML, Gordon LI, Lunning M, Wang M, Arnason J, et al. Two-year follow-up of lisocabtagene maraleucel in relapsed or refractory large B-cell lymphoma in TRANSCEND NHL 001. Blood. 2024;143(5):404-16. DOI: https://doi.org/10.1182/blood.2023020854
Alarcon Tomas A, Fein JA, Fried S, Flynn JR, Devlin SM, Fingrut WB, et al. Outcomes of first therapy after CD19-CAR-T treatment failure in large B-cell lymphoma. Leukemia. 2023;37(1):154-63. DOI: https://doi.org/10.1038/s41375-022-01739-2
Shumilov E, Scholz JK, Seib M, Mazzeo P, Wurm-Kuczera R, Vucinic V, et al. Outcomes of bispecific antibody therapy after CAR T-cell failure in relapsed/refractory large B-cell lymphoma. Blood Adv. 2025;9(15):3955-66. DOI: https://doi.org/10.1182/bloodadvances.2024015719
Cartron G, Houot R, Al Tabaa Y, Le Bras F, Ysebaert L, Choquet S, et al. Glofitamab in refractory or relapsed diffuse large B cell lymphoma after failing CAR-T cell therapy: a phase 2 LYSA study. Nat Cancer. 2025. DOI: https://doi.org/10.1038/s43018-025-00941-2
Crump M, Neelapu SS, Farooq U, Van Den Neste E, Kuruvilla J, Westin J, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800-8. DOI: https://doi.org/10.1182/blood-2017-03-769620
Crombie JL, Graff T, Falchi L, Karimi YH, Bannerji R, Nastoupil L, et al. Consensus recommendations on the management of toxicity associated with CD3xCD20 bispecific antibody therapy. Blood. 2024;143(16):1565-75. DOI: https://doi.org/10.1182/blood.2023022432
Fleury I, MacDonald D, Shafey M, Christofides A, Sehn LH. Optimal use of bispecific antibodies for the treatment of diffuse large B-cell lymphoma in Canada. Curr Oncol. 2025;32(3). DOI: https://doi.org/10.3390/curroncol32030142
MacDonald D, Puckrin R, Skrabek P, Lam S, Jayakar J, Fleury I, et al. Practical Guidance for the expanded implementation and provision of bispecific antibodies for diffuse large B-cell lymphoma (DLBCL) across Canada. Curr Oncol. 2025;32(8). DOI: https://doi.org/10.3390/curroncol32080460
Columvi Glofitamab injection Product Monograph. Hoffmann-La Roche Limited. Mississauga, ON; September 16, 2025.
Epkinly epcoritamab injection Product Monograph. AbbVie Corporation. St-Laurent, Quebec; April 2024.
Thieblemont C, Phillips T, Ghesquieres H, Cheah CY, Clausen MR, Cunningham D, et al. Epcoritamab, a novel, subcutaneous CD3xCD20 bispecific T-cell-engaging antibody, in relapsed or refractory large B-cell lymphoma: dose expansion in a Phase I/II trial. J Clin Oncol. 2023;41(12):2238-47. DOI: https://doi.org/10.1200/JCO.22.01725
Thieblemont C, Karimi YH, Ghesquieres H, Cheah CY, Clausen MR, Cunningham D, et al. Epcoritamab in relapsed/refractory large B-cell lymphoma: 2-year follow-up from the pivotal EPCORE NHL-1 trial. Leukemia. 2024;38(12):2653-62. DOI: https://doi.org/10.1038/s41375-024-02410-8
Brooks TR, Zabor EC, Bedelu Y, Yang X, Karimi YH, Nefved AN, et al; Real-world outcomes of patients with aggressive B-cell lymphoma treated with epcoritamab or glofitamab. Blood. Published online July 15, 2025.
Dickinson MJ, Carlo-Stella C, Morschhauser F, Bachy E, Corradini P, Iacoboni G, et al. glofitamab for relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2022;387(24):2220-31. DOI: https://doi.org/10.1056/NEJMoa2206913
Ayers EC, Margolis D, Landsburg DJ. Real world outcomes in patients with relapsed/refractory diffuse large B-cell lymphoma receiving palliative intent therapies. Clin Lymphoma Myeloma Leuk. 2020;20(10):661-7. DOI: https://doi.org/10.1016/j.clml.2020.05.008
Abramson JS, Ku M, Hertzberg M, Huang HQ, Fox CP, Zhang H, et al. 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;404(10466):1940-54. DOI: https://doi.org/10.1016/S0140-6736(24)01774-4
Marshalek JP, Qing X, Dragan M, Tomassetti S. Retrospective study of CD20 expression loss in relapsed or refractory B-cell non-hodgkin lymphoma. J Hematol. 2024;13(6):268-77. DOI: https://doi.org/10.14740/jh1341
Ferreri AJ, Dognini GP, Verona C, Patriarca C, Doglioni C, Ponzoni M. Re-occurrence of the CD20 molecule expression subsequent to CD20-negative relapse in diffuse large B-cell lymphoma. Haematologica. 2007;92(1):e1-2. DOI: https://doi.org/10.3324/haematol.10255
Hwang JP, Feld JJ, Hammond SP, Wang SH, Alston-Johnson DE, Cryer DR, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-715. DOI: https://doi.org/10.1200/JCO.20.01757
Vaidya R, Torres Lopez A, Awan F, Hrom J, Rivera-Rodriguez N, Lee EH, et al. ABCL-1224: Updated results from EPCORE NHL-6: phase 2 study of subcutaneous epcoritamab as outpatient treatment for 2L+ relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Clin Lymphoma Myeloma Leuk. 2025;25(supplement 1):S790-S1. DOI: https://doi.org/10.1016/S2152-2650(25)02359-6
Falchi L, Hutchings M, Carlo-Stella C, Morschhauser F, Dickinson M, Cartron G, et al. Dexamethasone is associated with reduced frequency and intensity of cytokine release syndrome compared with alternative corticosteroid regimens as premedication for glofitamab in patients with relapsed/refractory large B-cell lymphoma. Haematologica. 2025;110(4):999-1004. DOI: https://doi.org/10.3324/haematol.2024.286257
Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019;25(4):625-38. DOI: https://doi.org/10.1016/j.bbmt.2018.12.758
Crochet G, Iacoboni G, Couturier A, Bachy E, Iraola-Truchuelo J, Gastinne T, et al. Efficacy of CAR T-cell therapy is not impaired by previous bispecific antibody treatment in large B-cell lymphoma. Blood. 2024;144(3):334-8. DOI: https://doi.org/10.1182/blood.2024024526
Melody M, Gordon LI. Sequencing of cellular therapy and bispecific antibodies for the management of diffuse large B-cell lymphoma. Haematologica. 2024;109(10):3138-45. DOI: https://doi.org/10.3324/haematol.2024.285255
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