136
Views
0
CrossRef citations to date
0
Altmetric
Review

Bispecific antibodies in the treatment of relapsed/refractory large B-cell lymphoma

, , &
Pages 705-715 | Received 18 Jan 2024, Accepted 28 May 2024, Published online: 03 Jun 2024

References

  • Susanibar-Adaniya S, Barta SK. 2021 update on diffuse large B cell lymphoma: A review of current data and potential applications on risk stratification and management. Am J Hematol. 2021 May 1;96(5):617–629. doi: 10.1002/ajh.26151
  • González Barca E. Role of bispecific antibodies in relapsed/refractory diffuse large B-Cell lymphoma in the CART era. Front Immunol. 2022;13. doi: 10.3389/fimmu.2022.909008
  • Fisher RI, Gaynor ER, Dahlberg S, et al. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin’s lymphoma. N Engl J Med. 1993;328(14):1002–1006. doi: 10.1056/NEJM199304083281404
  • Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235–242. doi: 10.1056/NEJMoa011795
  • Tilly H, Morschhauser F, Sehn LH, et al. Polatuzumab vedotin in previously untreated diffuse large B-Cell lymphoma. N Engl J Med. 2022;386(4):351–363. doi: 10.1056/NEJMoa2115304
  • 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):1540–1545. doi: 10.1056/NEJM199512073332305
  • 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 Nov;20(11):1729–1736. doi: 10.1016/j.bbmt.2014.06.036
  • Costa LJ, Maddocks K, Epperla N, et al. Diffuse large B-cell lymphoma with primary treatment failure: Ultra-high risk features and benchmarking for experimental therapies. Am J Hematol. 2017 Feb;92(2):161–170. doi: 10.1002/ajh.24615
  • 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 Oct 19;130(16):1800–1808. doi: 10.1182/blood-2017-03-769620
  • 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 Sep 20;28(27):4184–4190. doi: 10.1200/JCO.2010.28.1618
  • GWv I, A M, 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):544–551. doi: 10.1200/JCO.2016.69.0198
  • 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):640–654. doi: 10.1056/NEJMoa2116133
  • Kamdar M, Solomon SR, Arnason JE, et al. COVID-19 in patients with CLL: improved survival outcomes and update on management strategies. Blood. 2021 Nov 23;138(18):1768–1773. doi: 10.1182/blood.2021011841
  • Chow VA, Gopal AK, Maloney DG, et al. Outcomes of patients with large B‐cell lymphomas and progressive disease following CD19‐specific CAR T‐cell therapy. Am J Hematol. 2019;94(8). doi: 10.1002/ajh.25505
  • Salles G, Duell J, González Barca E, et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol. 2020 Jul 0;21(7):978–988. doi: 10.1016/S1470-2045(20)30225-4
  • Sehn LH, Hertzberg M, Opat S, et al. Polatuzumab vedotin plus bendamustine and rituximab in relapsed/refractory DLBCL: survival update and new extension cohort data. Blood Adv. 2022;6(2):533–543. doi: 10.1182/bloodadvances.2021005794
  • Gouni S, Rosenthal AC, Crombie JL, et al. A multicenter retrospective study of polatuzumab vedotin in patients with large B-cell lymphoma after CAR T-cell therapy. Blood Adv. 2022 May 10;6(9):2757–2762. doi: 10.1182/bloodadvances.2021006801
  • Caimi PF, Ai W, Alderuccio JP, et al. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. The Lancet Oncology. 2021 Jun 1;22(6):790–800. doi: 10.1016/S1470-2045(21)00139-X
  • Falchi L, Vardhana SA, Salles GA. Bispecific antibodies for the treatment of B-cell lymphoma: promises, unknowns, and opportunities. Blood. 2023 Feb 2;141(5):467–480. doi: 10.1182/blood.2021011994
  • Iacoboni G, Serna A, Navarro Garces V, et al. Impact of prior bendamustine exposure on bispecific antibody treatment outcomes for patients with B-Cell lymphoma. Blood. 2023;142(Supplement 1):310–310. doi: 10.1182/blood-2023-184883
  • Iacoboni G, Martin Lopez AA, Jalowiec KA, 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. Blood. 2022;140(Supplement 1):1592–1594. doi: 10.1182/blood-2022-169783
  • Thieblemont C, Phillips T, Ghesquieres H, 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):2238–2247. doi: 10.1200/JCO.22.01725
  • Hutchings M, Mous R, Clausen MR, et al. Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study. Lancet. 2021;398(10306):1157–1169. doi: 10.1016/S0140-6736(21)00889-8
  • Li T, Gibiansky L, Parikh A, et al. Identification of optimal dosing regimen for subcutaneous epcoritamab in relapsed or refractory b-cell non-Hodgkin lymphoma. Blood. 2023;142(Supplement 1):3135–3135. doi: 10.1182/blood-2023-181322
  • Karimi Y, Ghesquieres H, Jurczak W, et al. Effect of follow-up time on the ability of subcutaneous epcoritamab to induce deep and durable complete remissions in patients with relapsed/refractory large B-cell lymphoma: Updated results from the pivotal EPCORE NHL-1 trial. J Clin Oncol. 2023;41(16_suppl):7525–7525. doi: 10.1200/JCO.2023.41.16_suppl.7525
  • Hutchings M, Morschhauser F, Iacoboni G, et al. Glofitamab, a novel, bivalent CD20-targeting T-cell-engaging bispecific antibody, induces durable complete remissions in relapsed or refractory B-Cell lymphoma: a phase I trial. J Clin Oncol. 2021 Jun 20;39(18):1959–1970. doi: 10.1200/JCO.20.03175
  • 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):2220–2231. doi: 10.1056/NEJMoa2206913
  • Hutchings M, Carlo-Stella C, Morschhauser F, et al. Glofitamab monotherapy in relapsed or refractory large B-Cell lymphoma: extended follow-up from a pivotal phase II study and subgroup analyses in patients with prior chimeric antigen Receptor T-Cell therapy and by baseline total metabolic tumor volume. Blood. 2023;142(Supplement 1):433–433. doi: 10.1182/blood-2023-173951
  • Bannerji R, Arnason JE, Advani RH, et al. Odronextamab, a human CD20xCD3 bispecific antibody in patients with CD20-positive B-cell malignancies (ELM-1): results from the relapsed or refractory non-Hodgkin lymphoma cohort in a single-arm, multicentre, phase 1 trial. Lancet Haematol. 2022 May;9(5):e327–e339. doi: 10.1016/S2352-3026(22)00072-2
  • Walewski J, Min Kim T, Cho S-G, et al. P1115: odronextamab in patients with relapsed/refractory diffuse large b-cell lymphoma: results from a prespecified analysis of the pivotal phase 2 study ELM-2. Hemasphere. 2023;7(S3):e50570ac. doi: 10.1097/01.HS9.0000971356.50570.ac
  • Zhu M, Conrado D, Srinivasan K, et al. Odronextamab monotherapy for the treatment of relapsed/refractory (R/R) follicular lymphoma (FL) and diffuse large B-Cell lymphoma (DLBCL): focus on clinical pharmacology and pharmacometrics in the ELM-1 and ELM-2 studies. Blood. 2023;142(Supplement 1):1436–1436. doi: 10.1182/blood-2023-180675
  • Crombie JL, Matasar M, Topp MS, et al. Odronextamab demonstrates durable complete responses in patients with diffuse large B-Cell lymphoma (DLBCL) progressing after CAR-T therapy: outcomes from the ELM-1 study. Blood. 2023 Nov 28;142:4461. doi: 10.1182/blood-2023-181602
  • Bartlett NL, Assouline S, Giri P, et al. Mosunetuzumab monotherapy is active and tolerable in patients with relapsed/refractory diffuse large B-cell lymphoma. Blood Adv. 2023 Sep 12;7(17):4926–4935. doi: 10.1182/bloodadvances.2022009260
  • Hou J-Z, Jacobs R, Cho S-G, et al. Interim results of the phase 1 study of tnb-486, a novel CD19xCD3 T-Cell engager, in patients with relapsed/refractory (R/R) B-NHL. Blood. 2022;140(Supplement 1):1474–1475. doi: 10.1182/blood-2022-166385
  • Patel K, Riedell PA, Tilly H, et al. A phase 1 study of plamotamab, an anti-CD20 x anti-CD3 bispecific antibody, in patients with relapsed/refractory non-Hodgkin’s lymphoma: recommended dose safety/efficacy update and escalation exposure-response analysis. Blood. 2022;140(Supplement 1):9470–9472. doi: 10.1182/blood-2022-159586
  • Budde E, Gopal AK, Flinn IW, et al. Preliminary results of a phase 1 dose escalation study of the first-in-class IgM based bispecific antibody Igm-2323 (anti-CD20 x anti-CD3) in patients with advanced B-Cell malignancies. Blood. 2020 Nov 05;136:45–46. doi: 10.1182/blood-2020-134983
  • Song Y, Li Z, Li L, et al. GB261, an Fc-function enabled and CD3 affinity de-tuned CD20/CD3 bispecific antibody, demonstrated a highly advantageous safety/efficacy balance in an ongoing first-in-human dose-escalation study in patients with relapsed/refractory non-Hodgkin lymphoma. Blood. 2023;142(Supplement 1):1719–1719. doi: 10.1182/blood-2023-188444
  • Zhang J, Zhou Z. Preclinical study of a novel tri-specific anti-CD3/CD19/CD20 T cell-engaging antibody as a potentially better treatment for NHL. Blood. 2020 Nov 5;136:22. doi: 10.1182/blood-2020-140154
  • Avivi Mazza I, Barba P, Yuda J, et al. A phase 1 study of PIT565, a first-in-class, anti-CD3, anti-CD19, anti-CD2 trispecific antibody in patients with relapsed and/or refractory B-Cell malignancies. Blood. 2023;142(Supplement 1):3099–3099. doi: 10.1182/blood-2023-179061
  • Shouse GP, Blum KA, Haydu JE, et al. A phase 1, open-label, dose escalation and dose expansion study of CLN-978 (CD19XCD3XHSA) in patients with relapsed/refractory (R/R) B-Cell non-Hodgkin lymphoma (B-NHL). Blood. 2023 Nov 28;142:3142. doi: 10.1182/blood-2023-181239
  • Budde LE, Olszewski AJ, Assouline S, et al. Mosunetuzumab plus polatuzumab vedotin demonstrates a favorable safety profile and efficacy in patients (Pts) with relapsed or refractory (R/R) large b-cell lymphoma (LBCL): primary analysis of a phase Ib/II study. Blood. 2023 Nov 28;142:613. doi: 10.1182/blood-2023-174209
  • Hess B, Li H, Hossain N, et al. SWOG 2114: a randomized phase ii trial of consolidation therapy followinG CD19 CAR T-CELL treatment for relapsed/refractory large B-CELL or grade IIIB follicular lymphoma. Hematol Oncol. 2023;41(S2):839–840. doi: 10.1002/hon.3166_OT19
  • Hutchings M, Sureda A, Terol MJ, et al. Glofitamab (Glofit) in combination with polatuzumab vedotin (Pola): phase Ib/II preliminary data support manageable safety and encouraging efficacy in relapsed/refractory (R/R) diffuse large B-Cell lymphoma (DLBCL). Blood. 2021;138(Supplement 1):525–525. doi: 10.1182/blood-2021-148359
  • Hutchings M, Carlo-Stella C, Gritti G, et al. CD19 4-1BBL (RO7227166) a novel costimulatory bispecific antibody can be safely combined with the t-cell-engaging bispecific antibody glofitamab in relapsed or refractory B-Cell non-Hodgkin Lymphoma. Blood. 2022;140(Supplement 1):9461–9463. doi: 10.1182/blood-2022-157011
  • Hertzberg M, Ku M, Catalani O, et al. A phase III trial evaluating glofitamab in combination with gemcitabine plus oxaliplatin versus rituximab in combination with gemcitabine and oxaliplatin in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). J Clin Oncol. 2021;39(15_suppl):TPS7575–TPS7575. doi: 10.1200/JCO.2021.39.15_suppl.TPS7575
  • Brody J, Joergensen JM, Belada D, et al. Epcoritamab SC + GemOx leads to high complete metabolic response rates in patients with relapsed/refractory diffuse large B-Cell lymphoma ineligible for autologous stem cell transplant: updated results from epcore NHL-2. Blood. 2023 Nov 28;142:3092. doi: 10.1182/blood-2023-180246
  • Avivi Mazza I, Kim WS, P-S K, et al. Subcutaneous epcoritamab plus lenalidomide in patients with relapsed/refractory diffuse large B-Cell lymphoma from EPCORE NHL-5. Blood. 2023 Nov 28;142(Supplement 1):438. doi: 10.1182/blood-2023-180089
  • Carpio C, Namuduri M, Iqbal N, et al. Trial in progress: phase 1 trial evaluating the safety and tolerability of odronextamab in combination with cemiplimab in relapsed/refractory aggressive B-Cell non-Hodgkin lymphoma. Blood. 2023 Nov 28;142:3100. doi: 10.1182/blood-2023-179964
  • Baird J, Mutsaers PG, Abramson JS, et al. Abstract CT129: trial in progress: ATHENA-1 - a phase 1, open-label, first-in-human study to assess safety and tolerability of REGN5837 in combination with odronextamab in patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphomas. Cancer Res. 2023;83(8_Supplement):CT129–CT129. doi: 10.1158/1538-7445.AM2023-CT129
  • Wei J, Montalvo-Ortiz W, Yu L, et al. CD22-targeted CD28 bispecific antibody enhances antitumor efficacy of odronextamab in refractory diffuse large B cell lymphoma models. Sci Transl Med. 2022 Nov 9;14(670):eabn1082. doi: 10.1126/scitranslmed.abn1082
  • Olszewski AJ, Phillips TJ, Hoffmann MS, et al. Mosunetuzumab in combination with CHOP in previously untreated DLBCL: safety and efficacy results from a phase 2 study. Blood Adv. 2023 Oct 24;7(20):6055–6065. doi: 10.1182/bloodadvances.2023010840
  • Olszewski AJ, Eradat H, Avigdor A, et al. Mosunetuzumab and polatuzumab vedotin demonstrates preliminary efficacy in elderly unfit/frail patients with previously untreated diffuse large B-Cell lymphoma. Blood. 2023 Nov 28;142:855. doi: 10.1182/blood-2023-177588
  • Topp MS, Tani M, Dickinson M, et al. Glofitamab plus R-CHOP induces high response rates and a favorable safety profile in patients with previously untreated diffuse large B-cell lymphoma (DLBCL): results from a phase ib study. Blood. 2022;140(Supplement 1):1775–1777. doi: 10.1182/blood-2022-157732
  • Dickinson M, Viardot A, Marks R, et al. Glofitamab + Pola-R-CHP in patients with previously untreated diffuse large B-cell lymphoma (DLBCL): results from a phase Ib study. J Clin Oncol. 2023;41(16_suppl):7549–7549. doi: 10.1200/JCO.2023.41.16_suppl.7549
  • Melchardt T, Wurm-Kuczera RI, Altmann B, et al. Feasibility and safety of the first-in-human chemotherapy-light combination of rituximab, polatuzumab vedotin and glofitamab in previously untreated aggressive b-cell lymphoma patients above 60 years of age ineligible for a fully dosed R-CHOP - R-Pola-Glo/Ikf-t062, a study of the Austrian group for medical tumor therapy (AGMT-NHL-16) and the German lymphoma alliance (GLA2022-10). Blood. 2023;142(Supplement 1):1734–1734.
  • Falchi L, Clausen M, Offner F, et al. Metabolic response rates of epcoritamab + R-CHOP in patients with previously untreated (1L) high-risk diffuse large B-cell lymphoma, including double-hit/triple-hit lymphoma: updated EPCORE NHL-2 data. J Clin Oncol. 2023;41(16_suppl):7519–7519. doi: 10.1200/JCO.2023.41.16_suppl.7519
  • Sehn LH, Chamuleau M, Lenz G, et al. Phase 3 trial of subcutaneous epcoritamab + R-CHOP versus R-CHOP in patients (pts) with newly diagnosed diffuse large B-cell lymphoma (DLBCL): EPCORE DLBCL-2. J Clin Oncol. 2023;41(16_suppl):TPS7592–TPS7592. doi: 10.1200/JCO.2023.41.16_suppl.TPS7592
  • Tessoulin B, Guidez S, Namuduri M, et al. PB2335: trial in progress: phase 3 trial evaluating the efficacy and safety of odronextamab plus CHOP (O-CHOP) versus R-CHOP in previously untreated diffuse large B-CELL lymphoma (OLYMPIA-3). Hemasphere. 2023;7(S3):e06798be. doi: 10.1097/01.HS9.0000976060.06798.be
  • Philipp N, Kazerani M, Nicholls A, et al. T-cell exhaustion induced by continuous bispecific molecule exposure is ameliorated by treatment-free intervals. Blood. 2022 Sep 8;140(10):1104–1118. doi: 10.1182/blood.2022015956
  • Piccione EC, Belousov A, Hamidi H, et al. P1210: immune correlates of response to glofitamab: biomarker findings from a pivotal phase II expansion study in patients with relapsed or refractory (R/R) diffuse large B-Cell lymphoma (DLBCL). Hemasphere. 2022;6:1096–1097. doi: 10.1097/01.HS9.0000847704.12245.1f
  • Raje N, Anderson K, Einsele H, et al. Monitoring, prophylaxis, and treatment of infections in patients with MM receiving bispecific antibody therapy: consensus recommendations from an expert panel. Blood Cancer J. 2023;13(1). doi: 10.1038/s41408-023-00879-7

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.