Therapy targeting CD19 antigen in diffuse large B-cell lymphoma

Czech version

Authors: V. Procházka ¹; V. Hanáčková ¹; L. Henzlová ²; P. Flodr ³; T. Papajík ¹
Authors‘ workplace: Hemato-onkologická klinika LF UP a FN Olomouc ¹; Klinika nukleární medicíny LF UP a FN Olomouc ²; Ústav klinické a molekulární patologie, LF UP a FN Olomouc ³
Published in: Transfuze Hematol. dnes,30, 2024, No. 1, p. 13-25.
Category: Review/Educational Papers
doi: https://doi.org/10.48095/cctahd2024prolekare.cz2

Overview

Diffuse large B-cell lymphoma (DLBCL) is the most common type of malignant lymphoma in the Czech Republic. It represents a very heterogeneous group of aggressive tumors with diverse biology, and varied clinical manifestations. The standard of therapy is based on immunotherapy targeted against the CD20 antigen of the tumor cells. The combination of the monoclonal antibody rituximab with chemotherapy has historically demonstrated a major benefit of cytotoxic immunity mechanisms in patients. This therapeutic concept, which has historically led to cure in nearly two-thirds of patients, has encountered its limits. Research into alternative immunotherapy approaches has led to the introduction of a generationally successful new class of drugs targeting the CD19 antigen with different mechanisms of action ranging from simple antibody action (tafasitamab) to antibody-drug conjugate (ADC) administration (loncastuximab-tesirine), to the formation of sophisticated CAR-T lymphocyte chimeric constructs (axicabtagene ciloleucel, tisagenlecleucel and lisocabtagene maraleucel). The review aims to summarize the findings of advanced medical research of new molecules, their sequences, and combinations with implications for therapeutic practice in the Czech Republic.

Keywords:

immunotherapy – Monoclonal antibodies – CD19 antigen – diff use large B-cell lymphoma

Sources

1. Alaggio R, Amador C, Anagnostopoulos I, et al. The 5th edition of the World Health Organization Classification of haematolymphoid tumours: lymphoid neoplasms [published cor- rection appears in Leukemia. 2023; 37 (9): 1944–1951]. Leukemia. 2022; 36 (7): 1720–1748.

2. Teras LR, DeSantis CE, Cerhan JR, Morton LM, Jemal A, Flowers CR. 2016 US lymphoid malignancy statistics by World Health Organization subtypes. CA Cancer J Clin. 2016; 66 (6): 443–459.

3. Trneny M, Campr V, Janikova A, et al. The improving outcome of non-Hodgkin lymphoma (NHL) within 15 years period-real world data of national-wide lymphoma project. Haematologica. 2016; 2016 (101): 479–480.

4. 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‘Adulte. Blood. 2010; 116 (12): 2040–2045.

5. 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.

6. Farooq U, Maurer MJ, Thompson CA, et al. Clinical heterogeneity of diffuse large B cell lymphoma following failure of front-line immunochemotherapy. Br J Haematol. 2017; 179 (1): 50–60.

7. Gisselbrecht C, Glass B, Mounier N, et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era [published correction appears in J Clin Oncol. 2012; 30 (15): 1896]. J Clin Oncol. 2010; 28 (27): 4184–4190.

8. Al-Mashhadi AL, Jakobsen LH, Brown P, et al. Real-world outcomes following third or subsequent lines of therapy: A Danish population-based study on 189 patients with relapsed/refractory large B-cell lymphomas. Br J Haematol. Published online November 27, 2023. doi: 10.1111/bjh.19201.

9. Rassy E, Danu A, Ibrahim T, et al. Outcomes of transplant-eligible patients with relapsed or refractory diffuse large B-cell lymphoma after second-line salvage chemotherapy: the Gustave Roussy experience. Clin Lymphoma Myeloma Leuk. 2021; 21 (4): e373–e380. doi: 10.1016/j.clml. 2020.11.008.

10. 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): 3490–3496.

11. Tun AM, Maliske S, Wang Y, et al. Progression-free survival at 24 months as a landmark after autologous stem cell transplant in relapsed or refractory diffuse large B-cell lymphoma. Transplant Cell Ther. 2022; 28 (9): 610–617.

12. Tedder TF, Isaacs CM. Isolation of cDNAs encoding the CD19 antigen of human and mouse B lymphocytes. A new member of the immunoglobulin superfamily. J Immunol. 1989; 143 (2): 712–717.

13. Wang K, Wei G, Liu D. CD19: a biomarker for B cell development, lymphoma diagnosis and therapy. Exp Hematol Oncol. 2012; 1 (1): 36. doi: 10.1186/2162-3619-1-36.

14. Visco C, Tanasi I, Quaglia FM, Ferrarini I, Fraenza C, Krampera M. Oncogenic mutations of MYD88 and CD79B in diffuse large B-cell lymphoma and implications for clinical practice. Cancers (Basel). 2020; 12 (10): 2913. https: //doi.org/10.3390/cancers12102913.

15. Young RM, Shaffer AL, 3rd, Phelan JD, Staudt LM. B-cell receptor signaling in diffuse large B-cell lymphoma. Semin Hematol. 2015; 52 (2): 77–85.

16. Raufi A, Ebrahim AS, Al‐Katib A. Targeting CD19 in B‐cell lymphoma: emerging role of SAR3419. Cancer Manag Res. 2013; 5: 225–233. doi: 10.2147/cmar.s45957 17.

18. Robkopf S, Eichholz KM, Winterberg D, et al. Enhancing CDC and ADCC of CD19 antibodies by combining Fc protein-engineering with Fc glyco-engineering. Antibodies (Basel). 2020; 9 (4): 63. doi: 10.3390/antib9040063.

19. Ramon Ortiz C, Wang S, Stathis A, et al. How to integrate CD19 specific chimeric antigen receptor T cells with other CD19 targeting agents in diffuse large B-cell lymphoma?. Hematol Oncol. Published online November 8, 2023. doi: 10.1002/hon.3237.

20. Horton HM, Bernett MJ, Pong E, et al. Potent in vitro and in vivo activity of an Fc‐engineered anti‐CD19 monoclonal antibody against lymphoma and leukemia. Cancer Res. 2008; 68 (19): 8049–8057. doi: 10.1158/0008‐5472.can‐08‐2268.

21. Awan FT, Lapalombella R, Trotta R, et al. CD19 targeting of chronic lymphocytic leukemia with a novel Fc‐domain‐engineered monoclonal antibody. Blood. 2010; 115 (6): 1204–1213.

22. Jurczak W, Zinzani PL, Hess G, et al. A Phase IIa, open‐label, multicenter study of single‐agent tafasitamab (MOR208), an Fcoptimized anti‐CD19 antibody, in patients with relapsed or refractory B‐cell non‐Hodgkin’s lymphoma: long‐term follow‐up, final analysis. Blood. 2019; 134 (Suppl 1): 4078.

23. Salles G, Duell J, Gonzalez Barca E, et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B‐cell lymphoma (LMIND): a multicentre, prospective, single‐arm, phase 2 study. Lancet Oncol. 2020; 21 (7): 978–988.

24. Gribben JG, Fowler N, Morschhauser F. Mechanisms of action of lenalidomide in B‐cell non‐Hodgkin lymphoma. J Clin Oncol. 2015; 33 (25): 2803–2811.

25. Belada D, Kopeckova K, Bergua Burgues JM, et al. Safety and efficacy of tafasitamab with or without lenalidomide added to first-line R-CHOP for DLBCL: the phase 1b First-MIND study. Blood. 2023; 142 (16): 1348–1358.

26. Duell J, Maddocks KJ, Gonzalez‐Barca E, et al. Long‐term outcomes from the phase II L‐MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory dif- fuse large B‐cell lymphoma. Haematologica. 2021; 106 (9): 2417–2426.

27. Nowakowski GS, Rodgers TD, Marino D, et al. RE‐MIND study: a propensity score‐based 1: 1 matched comparison of tafasitamab + lenalidomide (L‐MIND) versus lenalidomide monotherapy (realworld data) in transplant‐ineligible patients with relapsed/refractory (R/R) diffuse large B‐cell lymphoma (DLBCL). J Clin Oncol. 2020; 38 (15_Suppl): 8020.

28. Hammer O. CD19 as an attractive target for antibody‐based therapy. MAbs. 2012; 4 (5): 571–577.

29. Kahl BS, Hamadani M, Radford J, et al. A phase I study of ADCT‐402 (loncastuximab tesirine), a novel pyrrolobenzodiazepinebased antibody‐drug conjugate, in relapsed/refractory B‐cell non‐Hodgkin lymphoma. Clin Cancer Res. 2019; 25 (23): 6986–6994.

30. Jain N, Stock W, Zeidan A, et al. Loncastuximab tesirine, an anti‐CD19 antibody‐drug conjugate, in relapsed/refractory B‐cell acute lymphoblastic leukemia. Blood Adv. 2020; 4 (3): 449–457.

31. Zinzani PL, Caimi PF, Carlo‐Stella C, et al. LOTIS 2 follow‐up analysis: updated results from a phase 2 study of loncastuximab tesirine in relapsed or refractory diffuse large B‐cell lymphoma. Hematol Oncol. 2021; 39 (S2): 252.

32. Carlo-Stella C, Zinzani PL, Janakiram M, et al. Planned interim analysis of a phase 2 study of loncastuximab tesirine plus ibrutinib in patients with advanced diffuse large B-cell lymphoma (LOTIS-3). Blood. 2021; 138 (Suppl 1): 54.

33. Linhares Y, Gandhi MD, Chung M, Adeleye J, Ungar D, Hamandani M. Safety and antitumor activity study evaluating loncastuximab tesirine and rituximab versus immunochemotherapy in diffuse large B‐cell lymphoma. Blood. 2020; 136 (Suppl 1): 9–10.

34. Hamadani M, Radford J, Carlo‐Stella C, et al. Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory Bcell non‐Hodgkin lymphoma. Blood. 2021; 137 (19): 2634–2645.

35. Chavez JC, Bachmeier C, Kharfan-Dabaja MA. CAR T-cell therapy for B-cell lymphomas: clinical trial results of available products. Ther Adv Hematol. 2019; 10: 2040620719841581. doi: 10.1177/2040620719841581.

36. Abramson JS. Anti-CD19 CAR T-cell therapy for B-cell non-Hodgkin lymphoma. Transfus Med Rev. 2020; 34 (1): 29–33.

37. Locke FL, Ghobadi A, Jacobson CA, et al. Long‐term safety and activity of axicabtagene ciloleucel in refractory large B‐cell lymphoma (ZUMA‐1): a single‐arm, multicentre, phase 1–2 trial. Lancet Oncol. 2019; 20 (1): 31–42.

38. Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B‐cell lymphoma. N Engl J Med. 2019; 380 (1): 45–56.

39. Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B‐cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020; 396 (10254): 839–852.

40. Westin JR, Kersten MJ, Salles G, et al. Efficacy and safety of CD19‐directed CAR‐T cell therapies in patients with relapsed/refractory aggressive B‐cell lymphomas: observations from the JULIET, ZUMA‐1, and TRANSCEND trials. Am J Hematol. 2021; 96 (10): 1295–1312.

41. Westin JR, Oluwole OO, Kersten MJ, et al. Survival with axicabtagene ciloleucel in large B-cell lymphoma. N Engl J Med. 2023; 389 (2): 148–157.

42. Bishop MR, Dickinson M, Purtill D, et al. Second-line tisagenlecleucel or standard care in aggressive B-cell lymphoma. N Engl J Med. 2022; 386 (7): 629–639.

43. Kamdar M, Solomon SR, Arnason J, et al. TRANSFORM Investigators. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022; 399 (10343): 2294–2308.

44. Gordon LI, Liu FF, Braverman J, et al. Lisocabtagene maraleucel for second-line relapsed or refractory large B-cell lymphoma: patient-reported outcomes from the PILOT study. Haematologica. Published online August 31, 2023. doi: 10.3324/haematol.2023.283162.

45. Brooks TR, Caimi PF. A paradox of choice: Sequencing therapy in relapsed/refractory diffuse large B-cell lymphoma. Blood Rev. Published online October 28, 2023. doi: 10.1016/ j.blre.2023.101140.

46. Sauter CS, Matasar MJ, Meikle J, et al. Prognostic value of FDG-PET prior to autologous stem cell transplantation for relapsed and refractory diffuse large B-cell lymphoma. Blood. 2015; 125 (16): 2579–2581.

47. Shah NN, Ahn KW, Litovich C, et al. Is autologous transplant in relapsed DLBCL patients achieving only a PET+ PR appropriate in the CAR T-cell era? Blood. 2021; 137 (10): 1416–1423.

48. Caimi PF, Auberle C, Goparaju K, Baidoun F, Cashen AF, Hill BT. Outcomes of DLBCL patients achieving complete remission after R-ICE Chemoimmunotherapy. Blood. 2022; 140 (Suppl 1): 381–383.

49. Červená kniha. Léčebné postupy v hematologii 2023 – Česká hematologická společnost ČLS JEP (hematology.cz).

50. Qualls D, Buege MJ, Dao P, et al. Tafasitamab and lenalidomide in relapsed/refractory large B cell lymphoma (R/R LBCL): real world outcomes in a multicenter retrospective study. Blood. 2022; 140 (Suppl 1): 787–789.

51. Hamadani M, Liao L, Wilson L, Howarth A, Flores C, Chen L. Real-world outcomes in relapsed/refractory DLBCL patients who received polatuzumab vedotin PLUS bendamustine and rituximab or tafasitamab plus lenalidomide by line of therapy. Blood. 2022; 140 (Suppl 1): 8058–8060.

52. Smith SD, Lopedote P, Samara Y, et al. Polatuzumab vedotin for relapsed/refractory aggressive B-cell lymphoma: a multicenter post-marketing analysis. Clin Lymphoma Myeloma Leuk. 2021; 21 (3): 170–175.

53. Vodicka P, Benesova K, Janikova A, et al. Polatuzumab vedotin plus bendamustine and rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma in the real world. Eur J Haematol. 2022; 109 (2): 162–165.

54. Schuster SJ, Maziarz RT, Rusch ES, et al. Grading and management of cytokine release syndrome in patients treated with tisagenlecleucel in the JULIET trial. Blood Adv. 2020; 4 (7): 1432–1439.

55. Tang K, Nastoupil LJ. Real-world experiences of CAR T-cell therapy for large B-cell lymphoma: how similar are they to the prospective studies? J Immunother Precis Oncol. 2021; 4 (3): 150–159.

56. Riedell PA, Hwang WT, Nastoupil LJ, et al. Patterns of use, outcomes, and resource utilization among recipients of commercial axicabtagene ciloleucel and tisagenlecleucel for relapsed/refractory aggressive B cell lymphomas. Transplant Cell Ther. 2022; 28 (10): 669–676.

57. Iacoboni G, Villacampa G, Martinez-Cibrian N, et al. Real-world evidence of tisagenlecleucel for the treatment of relapsed or refractory large B-cell lymphoma. Cancer Med. 2021; 10 (10): 3214–3223.

58. Caimi PF, Hamadani M, Carlo-Stella C, et al. CD19 expression by IHC alone is not a predictor of response to Loncastuximab Tesirine: results from the LOTIS-2 clinical trial and quantitative systems pharmacology Modeling. Blood. 2022; 140 (Suppl 1): 9548–9550.

59. Fitzgerald KN, Quesada AE, von Keudell G, et al. CD19 epitope masking by tafasitamab leads to delays in subsequent use of CD19 CAR T-cell therapy in two patients with aggressive mature B-cell lymphomas. Leuk Lymphoma. 2022; 63 (3): 751–754.

60. Spiegel JY, Dahiya S, Jain MD, et al. Outcomes of patients with large B-cell lymphoma progressing after axicabtagene ciloleucel therapy. Blood. 2021; 137 (13): 1832–1835.

61. Thapa B, Caimi PF, Ardeshna KM, et al. CD19 antibody-drug conjugate therapy in DLBCL does not preclude subsequent responses to CD19-directed CAR T-cell therapy [published correction appears in Blood Adv. 2020; 4 (19): 4606]. Blood Adv. 2020; 4 (16): 3850–3852.

62. Sakemura R, Horvei P, Manriquez-Roman C, et al. The impact of prior treatment with a CD19 targeting monoclonal antibody on subsequent treatment with CD19 targeting CART cell therapy in preclinical models. Blood. 2021; 138 (Suppl 1): 2412.

63. 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.

64. 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.

65. Bannerji R, Arnason JE, Advani RH, et al. Odronextamab, a human CD20×CD3 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; 9 (5): e327–e339. doi: 10.1016/S2352-3026 (22) 00072-2.

66. Budde LE, Assouline S, Sehn LH, et al. Single-agent mosunetuzumab shows durable complete responses in patients with relapsed or refractory B-cell lymphomas: phase I dose-escalation study. J Clin Oncol. 2022; 40 (5): 481–491.

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Autoři děkují MUDr. Lence Henzlové, Ph.D, za přípravu obrazových podkladů vyšetření PET/CT a MUDr. Patriku Flodrovi, Ph.D., za přípravu fotodokumentace histologických preparátů.

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Do redakce doručeno dne: 4. 1. 2024.
Přijato po recenzi dne: 24. 1. 2024.

prof. MUDr. Vít Procházka, Ph.D.
Hemato-onkologická klinika
LF UP a FN Olomouc
Zdravotníků 248/7
779 00 Olomouc
e-mail: vit.prochazka@fnol.cz