An An Overview of the Treatment of Non-Hodgkin Lymphoma with The Novel Cellular Therapies: CAR-T and Bispecific Monoclonal Antibodies
Main Article Content
Abstract
The management of non-Hodgkin lymphoma (NHL), including refractory and relapsed high grade and low-grade NHL has been significantly improved in recent years with the development of cellular therapies which harness the powerful anti-cancer effects of the immune system. These include the ground-breaking and now established technology of chimeric antigen receptor cell therapy as well as the promising new range of bispecific monoclonal antibody therapies. This article will give a summary of the currently available cellular and bi-specific antibody therapies for the treatment of NHL in licenced use and clinical trials, including an overview of their proven efficacy and characteristic side-effect profiles which distinguish them from conventional immunochemotherapy. The relative strengths and weaknesses of these comparable therapies will also be discussed together with consideration of where they may fit into the treatment sequence of NHL in the future. The article will also address the challenges of delivering these innovative technologies in different healthcare settings and how they may alter the future of therapy for patients with this form of cancer.
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How to Cite
TUCKER, David; THIEBAUD, Cristina M..
An An Overview of the Treatment of Non-Hodgkin Lymphoma with The Novel Cellular Therapies: CAR-T and Bispecific Monoclonal Antibodies.
Medical Research Archives, [S.l.], v. 11, n. 9, sep. 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/4494>. Date accessed: 21 nov. 2024.
doi: https://doi.org/10.18103/mra.v11i9.4494.
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The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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12. Tilly H, Morschhauser F, Sehn LH, et al. The POLARIX Study: Polatuzumab Vedotin with Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (pola-R-CHP) Versus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP) Therapy in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma. Blood. 2021;138(Supplement 2):LBA-1. doi:10.1182/BLOOD-2021-154729
13. González-Barca E, Boumendil A, Blaise D, et al. Outcome in patients with diffuse large B-cell lymphoma who relapse after autologous stem cell transplantation and receive active therapy. A retrospective analysis of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplantation 2019 55:2. 2019;55(2):393-399. doi:10.1038/s41409-019-0650-x
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20. Gordon MJ, Smith MR, Nastoupil LJ. Follicular lymphoma: The long and winding road leading to your cure? Blood Rev. 2023;57:100992. doi:10.1016/J.BLRE.2022.100992
21. Patel A, Oluwole O, Savani B, Dholaria B. Taking a BiTE out of the CAR T space race. Br J Haematol. 2021;195(5):689-697. doi:10.1111/BJH.17622
22. Sterner RC, Sterner RM. CAR-T cell therapy: current limitations and potential strategies. Blood Cancer J. 2021;11(4):69. doi:10.1038/S41408-021-00459-7
23. Dagar G, Gupta A, Masoodi T, et al. Harnessing the potential of CAR-T cell therapy: progress, challenges, and future directions in hematological and solid tumor treatments. J Transl Med. 2023;21(1):449. doi:10.1186/S12967-023-04292-3
24. Salvaris R, Ong J, Gregory GP. Bispecific Antibodies: A Review of Development, Clinical Efficacy and Toxicity in B-Cell Lymphomas. J Pers Med. 2021;11(5). doi:10.3390/JPM11050355
25. Lejeune M, Köse MC, Duray E, Einsele H, Beguin Y, Caers J. Bispecific, T-Cell-Recruiting Antibodies in B-Cell Malignancies. Front Immunol. 2020;11:520058. doi:10.3389/FIMMU.2020.00762/BIBTEX
26. Lee DW, Santomasso BD, Locke FL, et al. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biology of Blood and Marrow Transplantation. 2019;25(4):625-638. doi:10.1016/j.bbmt.2018.12.758
27. Shimabukuro-Vornhagen A, Gödel P, Subklewe M, et al. Cytokine release syndrome. J Immunother Cancer. 2018;6(1):56. doi:10.1186/S40425-018-0343-9
28. Jain, M. D., Smith, M., & Shah, N. N. (2023). How I treat refractory CRS and ICANS after CAR T-cell therapy. Blood, 141(20), 2430–2442. https://doi.org/10.1182/BLOOD.2022017414
29. Perales MA, Anderson LD, Jain T, et al. Role of CD19 Chimeric Antigen Receptor T Cells in Second-Line Large B Cell Lymphoma: Lessons from Phase 3 Trials. An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy. Transplant Cell Ther. 2022;28(9):546-559. doi:10.1016/J.JTCT.2022.06.019
30. Neelapu SS, Jacobson CA, Ghobadi A, 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):2307-2315. doi:10.1182/BLOOD.2022018893/2035688/BLOOD.2022018893.PDF
31. Balke-Want H. Putting the pedal to the metal: axi-cel for LBCL. Blood. 2023;141(19):2285-2286. doi:10.1182/BLOOD.2023020188
32. 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. doi:10.1016/S1470-2045(18)30864-7
33. Jacobson CA, Locke FL, Ma L, et al. Real-World Evidence of Axicabtagene Ciloleucel for the Treatment of Large B Cell Lymphoma in the United States. Transplant Cell Ther. 2022;28(9):581.e1-581.e8. doi:10.1016/J.JTCT.2022.05.026
34. Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. New England Journal of Medicine. 2019;380(1):45-56. doi:10.1056/NEJMOA1804980/SUPPL_FILE/NEJMOA1804980_DISCLOSURES.PDF
35. 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. The Lancet. 2020;396 (10254):839-852. doi:10.1016/S0140-6736(20)31366-0
36. Kamdar M, Solomon SR, Arnason J, et al. 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. The Lancet. 2022;399(10343):2294-2308. doi:10.1016/S0140-6736(22)00662-6
37. Falchi L, Vardhana SA, Salles GA. Bispecific antibodies for the treatment of B-cell lymphoma: promises, unknowns, and opportunities. Blood. 2023;141(5):467-480. doi:10.1182/BLOOD.2021011994/1928283/BLOOD.2021011994.PDF
38. Salles G, Barrett M, Foà R, et al. Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience. Advances in Therapy 2017 34:10. 2017;34(10):2232-2273. doi:10.1007/S12325-017-0612-X
39. Bock AM, Nowakowski GS, Wang Y. Bispecific Antibodies for Non-Hodgkin Lymphoma Treatment. Curr Treat Options Oncol. 2022;23(2):155-170. doi:10.1007/S11864-021-00925-1/METRICS
40. 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. Journal of Clinical Oncology. 2021;39(18):1959-1970. doi:10.1200/JCO.20.03175
41. Budde LE, Sehn LH, Matasar M, et al. Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. Lancet Oncol. 2022;23(8):1055-1065. doi:10.1016/S1470-2045(22)00335-7
42. 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
43. Cusatis R, Tan I, Piehowski C, et al. Worsening Financial Toxicity Among Patients Receiving Chimeric Antigen Receptor t-Cell (CAR-T) Therapy: A Mixed Methods Longitudinal Study. Blood. 2021;138(Supplement 1):567-567. doi:10.1182/BLOOD-2021-146032
44. Chacim S, Monjardino T, Cunha JL, et al. Costs, effectiveness, and safety associated with Chimeric Antigen Receptor (CAR) T-cell therapy: Results from a comprehensive cancer center. PLoS One. 2022;17(12):e0278950. doi:10.1371/JOURNAL.PONE.0278950
2. Howlader N, Noone AM, Krapcho M, et al. Cancer Statistics Review, 1975-2017 - SEER Statistics. National Cancer Institute. Published November 2019. Accessed August 15, 2023. https://seer.cancer.gov/archive/csr/1975_2017/
3. Epperla N, Vaughn JL, Othus M, Hallack A, Costa LJ. Recent survival trends in diffuse large B-cell lymphoma––Have we made any progress beyond rituximab? Cancer Med. 2020;9(15):5519-5525. doi:10.1002/CAM4.3237
4. 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):1800-1808. doi:10.1182/BLOOD-2017-03-769620
5. Tan D, Horning SJ, Hoppe RT, et al. Improvements in observed and relative survival in follicular grade 1-2 lymphoma during 4 decades: the Stanford University experience. Blood. 2013;122(6):981-987. doi:10.1182/BLOOD-2013-03-491514
6. Casulo C, Byrtek M, Dawson KL, et al. Early relapse of follicular lymphoma after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone defines patients at high risk for death: An analysis from the National LymphoCare Study. Journal of Clinical Oncology. 2015;33(23):2516-2522. doi:10.1200/JCO.2014.59.7534
7. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375-2390. doi:10.1182/BLOOD-2016-01-643569
8. WHO » WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Accessed August 22, 2023. https://www.iarc.who.int/news-events/who-classification-of-tumours-of-haematopoietic-and-lymphoid-tissues-2/
9. Bowzyk Al-Naeeb A, Ajithkumar T, Behan S, Hodson DJ. Non-Hodgkin lymphoma. BMJ (Online). 2018;362. doi:10.1136/bmj.k3204
10. Vodicka P, Klener P, Trneny M. Diffuse Large B-Cell Lymphoma (DLBCL): Early Patient Management and Emerging Treatment Options. Onco Targets Ther. 2022;15:1481. doi:10.2147/OTT.S326632
11. Stegemann M, Denker S, Schmitt CA. DLBCL 1L—What to Expect beyond R-CHOP? Cancers (Basel). 2022;14(6). doi:10.3390/CANCERS14061453
12. Tilly H, Morschhauser F, Sehn LH, et al. The POLARIX Study: Polatuzumab Vedotin with Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (pola-R-CHP) Versus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP) Therapy in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma. Blood. 2021;138(Supplement 2):LBA-1. doi:10.1182/BLOOD-2021-154729
13. González-Barca E, Boumendil A, Blaise D, et al. Outcome in patients with diffuse large B-cell lymphoma who relapse after autologous stem cell transplantation and receive active therapy. A retrospective analysis of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplantation 2019 55:2. 2019;55(2):393-399. doi:10.1038/s41409-019-0650-x
14. 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):1800-1808. doi:10.1182/BLOOD-2017-03-769620
15. Westin J, Sehn LH. CAR T cells as a second-line therapy for large B-cell lymphoma: a paradigm shift? Blood. 2022;139(18):2737-2746. Blood. 2023;141(6):683-683. doi:10.1182/BLOOD.2022018793
16. 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
17. 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. The Lancet. 2021;398(10306):1157-1169. doi:10.1016/S0140-6736(21)00889-8
18. Wang Y, Zhou S, Qi X, et al. Efficacy of front-line immunochemotherapy for follicular lymphoma: a network meta-analysis of randomized controlled trials. Blood Cancer J. 2022;12(1):1. doi:10.1038/S41408-021-00598-X
19. Marcus R, Davies A, Ando K, et al. Obinutuzumab for the First-Line Treatment of Follicular Lymphoma. New England Journal of Medicine. 2017;377(14):1331-1344. doi:10.1056/NEJMOA1614598/SUPPL_FILE/NEJMOA1614598_DISCLOSURES.PDF
20. Gordon MJ, Smith MR, Nastoupil LJ. Follicular lymphoma: The long and winding road leading to your cure? Blood Rev. 2023;57:100992. doi:10.1016/J.BLRE.2022.100992
21. Patel A, Oluwole O, Savani B, Dholaria B. Taking a BiTE out of the CAR T space race. Br J Haematol. 2021;195(5):689-697. doi:10.1111/BJH.17622
22. Sterner RC, Sterner RM. CAR-T cell therapy: current limitations and potential strategies. Blood Cancer J. 2021;11(4):69. doi:10.1038/S41408-021-00459-7
23. Dagar G, Gupta A, Masoodi T, et al. Harnessing the potential of CAR-T cell therapy: progress, challenges, and future directions in hematological and solid tumor treatments. J Transl Med. 2023;21(1):449. doi:10.1186/S12967-023-04292-3
24. Salvaris R, Ong J, Gregory GP. Bispecific Antibodies: A Review of Development, Clinical Efficacy and Toxicity in B-Cell Lymphomas. J Pers Med. 2021;11(5). doi:10.3390/JPM11050355
25. Lejeune M, Köse MC, Duray E, Einsele H, Beguin Y, Caers J. Bispecific, T-Cell-Recruiting Antibodies in B-Cell Malignancies. Front Immunol. 2020;11:520058. doi:10.3389/FIMMU.2020.00762/BIBTEX
26. Lee DW, Santomasso BD, Locke FL, et al. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biology of Blood and Marrow Transplantation. 2019;25(4):625-638. doi:10.1016/j.bbmt.2018.12.758
27. Shimabukuro-Vornhagen A, Gödel P, Subklewe M, et al. Cytokine release syndrome. J Immunother Cancer. 2018;6(1):56. doi:10.1186/S40425-018-0343-9
28. Jain, M. D., Smith, M., & Shah, N. N. (2023). How I treat refractory CRS and ICANS after CAR T-cell therapy. Blood, 141(20), 2430–2442. https://doi.org/10.1182/BLOOD.2022017414
29. Perales MA, Anderson LD, Jain T, et al. Role of CD19 Chimeric Antigen Receptor T Cells in Second-Line Large B Cell Lymphoma: Lessons from Phase 3 Trials. An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy. Transplant Cell Ther. 2022;28(9):546-559. doi:10.1016/J.JTCT.2022.06.019
30. Neelapu SS, Jacobson CA, Ghobadi A, 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):2307-2315. doi:10.1182/BLOOD.2022018893/2035688/BLOOD.2022018893.PDF
31. Balke-Want H. Putting the pedal to the metal: axi-cel for LBCL. Blood. 2023;141(19):2285-2286. doi:10.1182/BLOOD.2023020188
32. 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. doi:10.1016/S1470-2045(18)30864-7
33. Jacobson CA, Locke FL, Ma L, et al. Real-World Evidence of Axicabtagene Ciloleucel for the Treatment of Large B Cell Lymphoma in the United States. Transplant Cell Ther. 2022;28(9):581.e1-581.e8. doi:10.1016/J.JTCT.2022.05.026
34. Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. New England Journal of Medicine. 2019;380(1):45-56. doi:10.1056/NEJMOA1804980/SUPPL_FILE/NEJMOA1804980_DISCLOSURES.PDF
35. 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. The Lancet. 2020;396 (10254):839-852. doi:10.1016/S0140-6736(20)31366-0
36. Kamdar M, Solomon SR, Arnason J, et al. 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. The Lancet. 2022;399(10343):2294-2308. doi:10.1016/S0140-6736(22)00662-6
37. Falchi L, Vardhana SA, Salles GA. Bispecific antibodies for the treatment of B-cell lymphoma: promises, unknowns, and opportunities. Blood. 2023;141(5):467-480. doi:10.1182/BLOOD.2021011994/1928283/BLOOD.2021011994.PDF
38. Salles G, Barrett M, Foà R, et al. Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience. Advances in Therapy 2017 34:10. 2017;34(10):2232-2273. doi:10.1007/S12325-017-0612-X
39. Bock AM, Nowakowski GS, Wang Y. Bispecific Antibodies for Non-Hodgkin Lymphoma Treatment. Curr Treat Options Oncol. 2022;23(2):155-170. doi:10.1007/S11864-021-00925-1/METRICS
40. 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. Journal of Clinical Oncology. 2021;39(18):1959-1970. doi:10.1200/JCO.20.03175
41. Budde LE, Sehn LH, Matasar M, et al. Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. Lancet Oncol. 2022;23(8):1055-1065. doi:10.1016/S1470-2045(22)00335-7
42. 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
43. Cusatis R, Tan I, Piehowski C, et al. Worsening Financial Toxicity Among Patients Receiving Chimeric Antigen Receptor t-Cell (CAR-T) Therapy: A Mixed Methods Longitudinal Study. Blood. 2021;138(Supplement 1):567-567. doi:10.1182/BLOOD-2021-146032
44. Chacim S, Monjardino T, Cunha JL, et al. Costs, effectiveness, and safety associated with Chimeric Antigen Receptor (CAR) T-cell therapy: Results from a comprehensive cancer center. PLoS One. 2022;17(12):e0278950. doi:10.1371/JOURNAL.PONE.0278950