Efficacy and Safety of Glofitamab Therapy in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A United Russian Experience Based on the Compassionate Use Program

Liudmila Valerevna Fedorova, N.B. Mikhailova, K.V. Lepik, A.M. Chekalov, O.G. Smykova, V.V. Markelov, G.S. Tumyan, A.A. Semenova, A.V. Arakelyan, L.S. Butaev, Iu.A. Oleinik, V.V. Ptushkin, Ya.K. Mangasarova, A.U. Magomedova, E.S. Gitelzon, N.G. Gabeeva, D.A. Koroleva, A.K. Smolianinova, E.E. Zvonkov, Iu.S. Osipov, N.V. Stepanova, T.V. Krinitsina, Yu.I. Podmankova, G.N. Khusainova, L.F. Mukharlyamova, O.R. Smirnova, I.V. Ishmatova, A.A. Zverkova, S.S. Elkhova, S.A. Volchenkov, I.S. Zyuzgin, D.D. Ivanova, E.A. Baryakh, E.N. Misyurina, P.A. Zeinalova, F.M. Abbasbeyli, O.L. Timofeeva, Yu.E. Ryabukhina, M.A. Ulyanova, V.V. Basmanova, T.N. Tsyganok, V.Yu. Kimaikina, S.V. Samarina, E.V. Zubkova, S.V. Ovanesyan, A.I. Iskhakova, A.Yu. Kuvshinov, A.A. Kuzyaeva, G.K. Isaeva, M.I. Andrievskikh, O.Yu. Arzhanukhina, T.V. Shelekhova, I.V. Morozova, P.V. Makarovskaya, O.S. Samoilova, I.V. Vasileva, A.Yu. Terekhova, N.A. Falaleeva, V.A. Shuvaev, S.V. Vlasova, V.A. Lapin, V.I. Bakhtina, A.D. Kulagin,

DOI:

https://doi.org/10.21320/2500-2139-2026-19-2-180-190

BACKGROUND. Clinical trials of glofitamab (Glofit) have demonstrated its high efficacy and tolerable toxicity profile in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) patients. However, the data on its use in a real-world setting remain sparse.

AIM. To assess the efficacy and safety of Glofit in the combined cohort of R/R DLBCL patients in a real-world setting in the Russian Federation.

MATERIALS & METHODS. This retrospective multi-center study enrolled 88 R/R DLBCL patients treated with Glofit under a compassionate use program from 2021 to 2024 in 22 Russian medical institutions. The median age of patients was 54 years (range 21–83 years), there were 42 (48 %) male patients. The main eligibility criteria were ≥ 3 prior therapy lines and exhaustion of available standard treatment methods. Glofit was administered as a monoregimen according to the schedule recommended in the package insert.

RESULTS. With the follow-up median of 8.4 months (range 0.6–52 months), overall response was achieved in 46 (53 %) patients including 36 (42 %) patients with complete response (CR). The median overall survival (OS) was 13.1 months (95% confidence interval [95% CI] from 8.6 months to not reached), the 1-year OS was 55.7 % (95% CI 45.6–68.1 %). The median progression-free survival (PFS) was 4.2 months (95% CI 2.8–8.8 months), and the 1-year PFS was 33.5 % (95% CI 24.6–45.8 %). The median OS and PFS in patients with CR was not reached, whereas the 1-year PFS and OS were 73.7 % (95% CI 59.4–91.5 %) and 87.9 % (95% CI 77.4–99.9 %), respectively. Adverse events (AEs) were reported in 75 (85 %) patients, among them AEs of grade ≥ 3 in 35 (40 %) patients. Cytokine release syndrome was identified in 33 (38 %) patients, and “flare” syndrome was registered in 14 (16 %) patients. Infectious complications were observed in 45 (51 %) patients. Grade 5 AEs included only COVID-19 infection (n = 7; 8 %). Male gender, early relapse/refractoriness as well as 3-month administration of bendamustine prior to Glofit therapy were associated with the rate of achieving CR. PFS was lower in bendamustine recipients and also in cases with B-symptoms and massive tumor (bulky, > 7.5 cm).

CONCLUSION. Glofit demonstrated high efficacy and tolerable toxicity profile in the treatment of R/R DLBCL patients. The results obtained in a real-world setting confirm the data from previously published clinical trials.

  1. Coiffier B, Thieblemont C, Van Den Neste E, et al. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d’Etudes des Lymphomes de l’Adult. Blood. 2010;116(12):2040–5. doi: 10.1182/blood-2010-03-276246. DOI: https://doi.org/10.1182/blood-2010-03-276246
  2. McMillan AK, Phillips EH, Kirkwood AA, et al. Favourable outcomes for high-risk diffuse large B-cell lymphoma (IPI 3–5) treated with front-line R-CODOX-M/R-IVAC chemotherapy: results of a phase 2 UK NCRI trial. Ann Oncol. 2020;31(9):1251–9. doi: 10.1016/j.annonc.2020.05.016. DOI: https://doi.org/10.1016/j.annonc.2020.05.016
  3. Bartlett NL, Wilson WH, Jung SH, et al. Dose-adjusted EPOCH-R compared with R-CHOP as frontline therapy for diffuse large B-cell lymphoma: clinical outcomes of the phase III intergroup trial Alliance/CALGB 50303. J Clin Oncol. 2019;37(21):1790–9. doi: 10.1200/JCO.18.01994. DOI: https://doi.org/10.1200/JCO.18.01994
  4. Harrysson S, Eloranta S, Ekberg S, et al. Incidence of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) including CNS relapse in a population-based cohort of 4243 patients in Sweden. Blood Cancer J. 2021;11(1):9. doi: 10.1038/s41408-020-00403-1. DOI: https://doi.org/10.1038/s41408-020-00403-1
  5. Gisselbrecht C, Glass B, Mounier N, et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010;28(27):4184–90. doi: 10.1200/JCO.2010.28.1618. DOI: https://doi.org/10.1200/JCO.2010.28.1618
  6. Crump M, Kuruvilla J, Couban S, et al. Randomized Comparison of Gemcitabine, Dexamethasone, and Cisplatin Versus Dexamethasone, Cytarabine, and Cisplatin Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed and Refractory Aggressive Lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014;32(31):3490–6. doi: 10.1200/JCO.2013.53.9593. DOI: https://doi.org/10.1200/JCO.2013.53.9593
  7. Van Imhoff GW, McMillan A, Matasar MJ, et al. Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma: The ORCHARRD Study. J Clin Oncol. 2017;35(5):544–51. doi: 10.1200/JCO.2016.69.0198. DOI: https://doi.org/10.1200/JCO.2016.69.0198
  8. Philip T, Guglielmi C, Hagenbeek A, 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: 10.1056/NEJM199512073332305. DOI: https://doi.org/10.1056/NEJM199512073332305
  9. Hamadani M, Hari PN, Zhang Y, et al. Early failure of frontline rituximab-containing chemo-immunotherapy in diffuse large B cell lymphoma does not predict futility of autologous hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2014; 20(11):1729–36. doi: 10.1016/j.bbmt.2014.06.036. DOI: https://doi.org/10.1016/j.bbmt.2014.06.036
  10. Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800–8. doi: 10.1182/blood-2017-03-769620. DOI: https://doi.org/10.1182/blood-2017-03-769620
  11. Bachy E, Le Gouill S, Di Blasi R, et al. A real-world comparison of tisagenlecleucel and axicabtagene ciloleucel CAR T cells in relapsed or refractory diffuse large B cell lymphoma. Nat Med. 2022;28(10):2145–2154. doi: 10.1038/s41591-022-01969-y. DOI: https://doi.org/10.1038/s41591-022-01969-y
  12. Bastos-Oreiro M, Abrisqueta P, Gutierrez A, et al. New therapies for relapsed or refractory aggressive B-cell lymphoma increase survival: Analysis from the RELINF registry of the GELTAMO group. Hemasphere. 2024;8(4):e70. doi: 10.1002/hem3.70. DOI: https://doi.org/10.1002/hem3.70
  13. Kamdar M, Solomon SR, Arnason JE, et al. Lisocabtagene Maraleucel (liso-cel), a CD19-Directed Chimeric Antigen Receptor (CAR) T Cell Therapy, Versus Standard of Care (SOC) with Salvage Chemotherapy (CT) Followed By Autologous Stem Cell Transplantation (ASCT) As Second-Line (2L) Treatment in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL): Results from the Randomized Phase 3 Transform Study. Blood. 2021;138(Suppl 1):91. doi: 10.1016/S0140-6736(22)00662-6. DOI: https://doi.org/10.1016/S0140-6736(22)00662-6
  14. Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma. N Engl J Med. 2022;386(7):640–54. doi: 10.1056/NEJMoa2116133.
  15. John S, Pulsipher MA, Moskop A, et al. Real-world outcomes for pediatric and young adult patients with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (ALL) treated with tisagenlecleucel: update from the center for international blood and marrow transplant research (CIBMTR) registry. Blood. 2021;138(Suppl 1):428. doi: 10.1182/blood-2021-146393. DOI: https://doi.org/10.1182/blood-2021-146393
  16. Hu B, Vaidya R, Ahmed F, et al. Real-World Analysis of Barriers to Timely Administration of Chimeric Antigen Receptor T Cell (CAR T) Therapy in Diffuse Large B-cell Lymphoma. Transplant Cell Ther. 2024;30(11):1082.e1–1082.e10. doi: 10.1016/j.jtct.2024.09.007. DOI: https://doi.org/10.1016/j.jtct.2024.09.007
  17. Falchi L, Vardhana SA, Salles GA. Bispecific antibodies for the treatment of B-cell lymphoma: promises, unknowns, and opportunities. Blood. 2023;141(5):467–80. doi: 10.1182/blood.2021011994. DOI: https://doi.org/10.1182/blood.2021011994
  18. Chu SY, Lee S-H, Rashid R, et al. Immunotherapy with long-lived anti-CD20×anti-CD3 bispecific antibodies stimulates potent T cell-mediated killing of human B cell lines and of circulating and lymphoid B cells in monkeys: a potential therapy for B cell lymphomas and leukemias. Blood. 2014;124(21):3111. doi: 10.1182/blood.V124.21.3111.3111. DOI: https://doi.org/10.1182/blood.V124.21.3111.3111
  19. Sun LL, Ellerman D, Mathieu M, et al. Anti-CD20/CD3 T cell-dependent bispecific antibody for the treatment of B cell malignancies. Sci Transl Med. 2015;7(287):287ra70. doi: 10.1126/scitranslmed.aaa4802. DOI: https://doi.org/10.1126/scitranslmed.aaa4802
  20. Bacac M, Colombetti S, Herter S, et al. CD20-TCB with Obinutuzumab Pretreatment as Next-Generation Treatment of Hematologic Malignancies. Clin Cancer Res. 201;24(19):4785–97. doi: 10.1158/1078-0432.CCR-18-0455. DOI: https://doi.org/10.1158/1078-0432.CCR-18-0455
  21. Dickinson MJ, Carlo-Stella C, Morschhauser F, et al. Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med. 2022;387(24):2220–31. doi: 10.1056/NEJMoa2206913. DOI: https://doi.org/10.1056/NEJMoa2206913
  22. Dickinson MJ, Carlo-Stella C, Morschhauser F, et al. Fixed-Duration Glofitamab Monotherapy Continues to Demonstrate Durable Responses in Patients with Relapsed or Refractory Large B-Cell Lymphoma: 3-Year Follow-up from a Pivotal Phase II Study. Blood. 2024;144(Suppl 1):865. doi: 10.1182/blood-2024-194333. DOI: https://doi.org/10.1182/blood-2024-194333
  23. Shumilov E, Wurm-Kuczera R, Kerkhoff A, et al. Safety and efficacy of glofitamab for relapsed/refractory large B-cell lymphoma in a multinational real-world study. Blood Adv. 2025;9(15):3865–77. doi: 10.1182/bloodadvances.2024014903. DOI: https://doi.org/10.1182/bloodadvances.2024014903
  24. Brooks TR, Zabor EC, Bedelu Y, et al. Real-world outcomes of patients with aggressive B-cell lymphoma treated with epcoritamab or glofitamab. Blood. 2025;146(18):2177–88. doi: 10.1182/blood.2025029117. DOI: https://doi.org/10.1182/blood.2025029117
  25. Birtas Atesoglu E, Gulbas Z, Uzay A, et al. Glofitamab in relapsed/refractory diffuse large B-cell lymphoma: Real-world data. Hematol Oncol. 2023;41(4):663–73. doi: 10.1002/hon.3174. DOI: https://doi.org/10.1002/hon.3174
  26. Федорова Л.В., Лепик К.В., Смыкова О.Г. и др. Прогноз пациентов с агрессивными В-НХЛ, достигших полного ответа на терапию биспецифическим CD20/CD3 антителом глофитамабом. Клеточная терапия и трансплантация. 2025;14(приложение 2):50–1. [Fedorova L.V., Lepik K.V., Smykova O.G., et al. Prognosis of aggressive B-NHL patients with complete response to bispecific CD20/CD3 antibody glofitamab therapy. Cellular Therapy and Transplantation. 2025;14(Suppl 2):50–1. (In Russ)]
  27. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas. Version 2.2025. Available at: https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf (accessed 14.11.2025).
  28. Abramson JS, Ku M, Hertzberg M, 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: 10.1016/S0140-6736(24)01774-4. DOI: https://doi.org/10.1016/S0140-6736(24)01774-4
  29. Minson A, Verner E, Giri P, et al. A Randomized Phase 2, Investigator-Led Trial of Glofitamab-R-CHOP or Glofitamab-Polatuzumab Vedotin-R-CHP (COALITION) in Younger Patients with High Burden, High-Risk Large B-Cell Lymphoma Demonstrates Safety, Uncompromised Chemotherapy Intensity, a High Rate of Durable Remissions, and Unique FDG-PET Response Characteristics. Blood. 2024;144(Suppl 1):582. doi: 10.1182/blood-2024-204930. DOI: https://doi.org/10.1182/blood-2024-204930
  30. Falchi L, Offner F, de Vos S, et al. Fixed-Duration Epcoritamab + R-CHOP Induces High Complete Response Rates in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma With High-Risk Features: Long-Term Results from the Epcore NHL-2 Trial. Blood. 2024;144(Suppl 1):581. doi: 10.1182/blood-2024-198023. DOI: https://doi.org/10.1182/blood-2024-198023
  31. Worel N, Mooyaart JE, Hoogenboom JD, et al. CAR-T cell manufacturing failures and out-of-specification products in the real-world setting: A survey from the EBMT cellular therapy and immunobiology working party. Bone Marrow Transplant. 2025;60(8):1184–6. doi: 10.1038/s41409-025-02623-0.
  32. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for Initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32(27):3059–68. doi: 10.1200/JCO.2013.54.8800. DOI: https://doi.org/10.1200/JCO.2013.54.8800
  33. Longhitano AP, Slavin MA, Harrison SJ, Teh BW. Bispecific antibody therapy, its use and risks for infection: Bridging the knowledge gap. Blood Rev. 2021;49:100810. doi: 10.1016/j.blre.2021.100810. DOI: https://doi.org/10.1016/j.blre.2021.100810
  34. Reynolds GK, Maclean M, Cliff ERS, et al. Infections in patients with lymphoma treated with bispecific antibodies: a systematic review and meta-analysis. Blood Adv. 2024;8(13):3555–9. doi: 10.1182/bloodadvances.2024012916. DOI: https://doi.org/10.1182/bloodadvances.2024012916
  35. Chaganti S, Dulobdas V, Wilson MR, et al. Clinical management of bispecific antibody therapy for lymphoma: A British Society for Haematology Good Practice Paper. Br J Haematol. 2025;207(4):1227–41. doi: 10.1111/bjh.70018. DOI: https://doi.org/10.1111/bjh.70018
  36. Iacoboni G, Navarro V, Martín-López AÁ, et al. Recent Bendamustine Treatment Before Apheresis Has a Negative Impact on Outcomes in Patients With Large B-Cell Lymphoma Receiving Chimeric Antigen Receptor T-Cell Therapy. J Clin Oncol. 2024;42(2):205–17. doi: 10.1200/JCO.23.01097. DOI: https://doi.org/10.1200/JCO.23.01097
  37. Phillips TJ, Clausen MR, Jurczak W, et al. Prior Bendamustine (Benda) Exposure Did Not Impact Clinical Outcomes and Decreased CD4+ but Not CD8+ T-Cells in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Treated with the Bispecific Antibody Epcoritamab (Epcor). Blood. 2024;144(Suppl 1):3115. doi: 10.1182/blood-2024-199799. DOI: https://doi.org/10.1182/blood-2024-199799
  38. Worel N, Mooyaart JE, Hoogenboom JD, et al. CAR-T cell manufacturing failures and out-of-specification products in the real-world setting: A survey from the EBMT cellular therapy and immunobiology working party. Bone Marrow Transplant. 2025;60(8):1184–6. doi: 10.1038/s41409-025-02623-0. DOI: https://doi.org/10.1038/s41409-025-02623-0
  39. Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma. N Engl J Med. 2022;386(7):640–54. doi: 10.1056/NEJMoa2116133. DOI: https://doi.org/10.1056/NEJMoa2116133

Keywords:

diffuse large B-cell lymphoma, bispecific antibodies, glofitamab, refractoriness, relapses, toxicity

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  • Liudmila Valerevna Fedorova,  , RM Gorbacheva Research Institute, Pavlov University, 6/8 L’va Tolstogo ul., Saint Petersburg, Russian Federation, 197022, e-mail: md.FedorovaL@gmail.com
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01.04.2026

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Vol. 19 No. 2 (2026)
LYMPHOID TUMORS

How to Cite

Fedorova L.V., Mikhailova N.B., Lepik K.V., et al. Efficacy and Safety of Glofitamab Therapy in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A United Russian Experience Based on the Compassionate Use Program. Clinical Oncohematology. Basic Research and Clinical Practice. 2026;19(2):180–190. doi:10.21320/2500-2139-2026-19-2-180-190.

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