Chimeric antigen receptor T-cell therapy for relapsed and refractory large B-cell lymphoma
A Canadian perspective
DOI:
https://doi.org/10.58931/cht.2022.1214Abstract
Comprising approximately 40% of diagnoses, lymphoma is the most common hematological malignancy in Canada, and 80% of lymphoma cases are non-Hodgkin lymphoma (NHL). Diffuse large B-cell lymphoma (DLBCL) accounts for approximately 30% of new NHL cases in Canada. First-line treatment with standard of care chemoimmunotherapy consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) results in a cure in approximately 60–70% of patients. Nevertheless, 30–40% of patients will experience relapse of their disease or are refractory to first-line therapy.
Among those patients with relapsed or refractory DLBCL (R/R DLBCL), about 10–15% will exhibit primary refractory disease with either stable or progressive disease despite first-line therapy, while 20–25% will experience relapse after an initial response to treatment. Most relapses will occur within 2–3 years following initial treatment. For these patients, the standard approach is salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) for those who meet the eligibility criteria and have chemosensitive disease.
References
Abramson JS, Palomba ML, Gordon LI, Lunning MA, Wang ML, et al. Pivotal safety and efficacy results from Transcend NHL 001, a multicenter phase 1 dtudy of lisocabtagene maraleucel (liso-cel) in relapsed/refractory (R/R) large B cell lymphomas. Blood. 2019;134(Suppl 1):241. doi:10.1182/blood-2019-127508 DOI: https://doi.org/10.1182/blood-2019-127508
Sarkozy C, Sehn LH. Management of relapsed/refractory DLBCL. Best Pract Res Clin Haematol. 2018 Sep;31(3):209-216. doi:10.1016/j.beha.2018.07.014 DOI: https://doi.org/10.1016/j.beha.2018.07.014
Sehn LH, Gascoyne RD. Diffuse large B-cell lymphoma: optimizing outcome in the context of clinical and biologic heterogeneity. Blood. 2015 Jan 1;125(1):22-32. doi:10.1182/blood-2014-05-577189 DOI: https://doi.org/10.1182/blood-2014-05-577189
Alberti G, Zimmet P, Shaw J, Grundy SM. The IDF consensus worldwide definition of the metabolic syndrome. International Diabetes Federation. 2006 [updated 2020 Jul 29; accessed 2021 Oct 30]. https://www.idf.org/e-library/consensus-statements/60-idfconsensus-worldwide-definitionof-the-metabolic-syndrome.
Sehn LH, Donaldson J, Chhanabhai M, Fitzgerald C, Gill K, Klasa R, et al. Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. J Clin Oncol. 2005;23(22):5027–33. doi:10.1200/JCO.2005.09.137 DOI: https://doi.org/10.1200/JCO.2005.09.137
Bachanova V, Perales MA, Abramson JS. Modern management of relapsed and refractory aggressive B-cell lymphoma: A perspective on the current treatment landscape and patient selection for CAR T-cell therapy. Blood Rev. 2020 Mar 1;40:100640. doi:10.1016/j.blre.2019.100640 DOI: https://doi.org/10.1016/j.blre.2019.100640
Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, 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 Nov 1;32(31):3490–6. doi:10.1200/JCO.2013.53.9593 DOI: https://doi.org/10.1200/JCO.2013.53.9593
Glass B, Dohm AJ, Truemper LH, Pfreundschuh M, Bleckmann A, Wulf GG, et al. Refractory or relapsed aggressive B-cell lymphoma failing (R)-CHOP: an analysis of patients treated on the RICOVER-60 trial. Ann Oncol Off J Eur Soc Med Oncol. 2017 Dec 1;28(12):3058–64. doi:10.1093/annonc/mdx556 DOI: https://doi.org/10.1093/annonc/mdx556
Gisselbrecht C, Glass B, Mounier N, Gill DS, Linch DC, Trneny M, 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):4184–90. doi:10.1200/JCO.2010.28.1618 DOI: https://doi.org/10.1200/JCO.2010.28.1618
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 Dec 7;333(23):1540–5. doi:10.1056/NEJM199512073332305 DOI: https://doi.org/10.1056/NEJM199512073332305
Mounier N, Canals C, Gisselbrecht C, Cornelissen J, Foa R, Conde E, et al. High-dose therapy and autologous stem cell transplantation in first relapse for diffuse large B cell lymphoma in the rituximab era: an analysis based on data from the European Blood and Marrow Transplantation Registry. Biol Blood Marrow Transplant. 2012 May 1;18(5):788–93. doi:10.1016/j.bbmt.2011.10.010 DOI: https://doi.org/10.1016/j.bbmt.2011.10.010
Chahoud J, Sui D, Erwin WD, Gulbis AM, Korbling M, Zhang M, et al. Updated Results of Rituximab Pre- and Post-BEAM with or without 90 Yttrium Ibritumomab Tiuxetan during Autologous Transplant for Diffuse Large B-cell Lymphoma. Clin Cancer Res. 2018 May 15;24(10):2304–11. doi:10.1158/1078-0432.CCR-17-3561 DOI: https://doi.org/10.1158/1078-0432.CCR-17-3561
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 Oct 19;130(16):1800–8. doi:10.1182/blood-2017-03-769620 DOI: https://doi.org/10.1182/blood-2017-03-769620
Jain T, Bar M, Kansagra AJ, Chong EA, Hashmi SK, Neelapu SS, et al. Use of Chimeric Antigen Receptor T Cell Therapy in Clinical Practice for Relapsed/Refractory Aggressive B Cell Non-Hodgkin Lymphoma: An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy. Biol Blood Marrow Transplant. 2019;25(12). doi:10.1016/j.bbmt.2019.08.015 DOI: https://doi.org/10.1016/j.bbmt.2019.08.015
Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N Engl J Med. 2017 Dec 28;377(26):2531–44. doi:10.1056/NEJMoa1707447 DOI: https://doi.org/10.1056/NEJMoa1707447
Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, et al. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med. 2019 Jan 3;380(1):45–56. doi:10.1056/NEJMoa1804980 DOI: https://doi.org/10.1056/NEJMoa1804980
Jacobson C. Long-Term (4- and 5-Year) Overall Survival in ZUMA-1, the Pivotal Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Refractory Large B-Cell Lymphoma (LBCL). Poster presented at: ASH 2021. 63rd American Society of Hematology Annual Meeting; 2021 Dec 11–14. Abstract 1764.
Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Reagan PM, Miklos DB, et al. Comparison of 2-year outcomes with CAR T cells (ZUMA-1) vs salvage chemotherapy in refractory large B-cell lymphoma. Blood Adv. 2021 Oct 26;5(20):4149–55. doi:10.1182/bloodadvances.2020003848 DOI: https://doi.org/10.1182/bloodadvances.2020003848
Locke FL, Miklos DB, Jacobson CA, Perales M-A, Kersten M-J, Oluwole OO, et al. Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma. N Engl J Med [online ahead of print]. 2021 Dec 11 [cited 2022 Feb 13];386:640-654. doi:10.1056/NEJMoa2116133 DOI: https://doi.org/10.1056/NEJMoa2116133
Kamdar M. 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. Presented at: ASH 2021. 63rd American Society of Hematology Annual Meeting; 2021 Dec 11–14. Abstract 91.
Bishop MR, Dickinson M, Purtill D, Barba P, Santoro A, Hamad N, et al. Second-Line Tisagenlecleucel or Standard Care in Aggressive B-Cell Lymphoma. N Engl J Med [online ahead of print]. 2021 Dec 14 [cited 2022 Feb 13];386:629-639. doi:10.1056/NEJMoa2116596 DOI: https://doi.org/10.1056/NEJMoa2116596
Nastoupil LJ, Jain MD, Feng L, Spiegel JY, Ghobadi A, Lin Y, et al. Standard-of-care axicabtagene ciloleucel for relapsed or refractory large B-cell lymphoma: Results from the US lymphoma CAR T consortium. J Clin Oncol. 2020 Sep 20;38(27):3119–28. DOI: https://doi.org/10.1200/JCO.19.02104
Shafey M, Savage KJ, Skrabek P, Elsawy M, Bosch M, Kuruvilla J. Canadian Evidence-Based Guideline for the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma. Lymphoma Canada. 2021 Sept 24.
Sehn LH, Herrera AF, Flowers CR, Manali KK, McMillan A, et al. Polatuzumab vedotin in relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol. 2020 Jan 10;38(2):155-165. doi:10.1200/JCO.19.00172 DOI: https://doi.org/10.1200/JCO.19.00172
Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, et al. Chimeric antigen receptor T-cell therapy — assessment and management of toxicities. Nat Rev Clin Oncol. 2017 Sept 19;15(1):47–62. doi:10.1038/nrclinonc.2017.148 DOI: https://doi.org/10.1038/nrclinonc.2017.148
Messmer AS, Que YA, Schankin C, Banz Y, Bacher U, Novak U, et al. CAR T-cell therapy and critical care: A survival guide for medical emergency teams. Wien Klin Wochenschr. 2021 Dec 1;133(23–24):1318–25. doi:10.1007/s00508-021-01948-2 DOI: https://doi.org/10.1007/s00508-021-01948-2
Azoulay E, Shimabukuro-Vornhagen A, Darmon M, Von Bergwelt-Baildon M. Critical care management of chimeric antigen receptor T cell-related toxicity: be aware and prepared. Am J Respir Crit Care Med. 2019 Jul 1;200(1):20–3. doi:10.1164/rccm.201810-1945ED DOI: https://doi.org/10.1164/rccm.201810-1945ED