Cellular therapy in CLL/iNHL: Therapeutic agents in the pipeline
DOI:
https://doi.org/10.58931/cht.2023.2232Abstract
Advanced cellular therapies have been introduced in Canada over the past two years. Chimeric antigen receptor (CAR) T-cell therapy is the current standard of care for third-line large B-cell lymphoma (LBCL), relapsed/ refractory (RR) acute lymphoblastic leukemia (ALL) in patients < 26 years old and, more recently, in third-line mantle cell lymphoma. These novel therapies are now gaining more prominence in the treatment of LBCL with recent FDA approval for the second line in patients eligible for stem cell transplant, based on recent Phase 3 trials. Another class of novel immunotherapy agents are bispecific T-cell engagers (BiTEs) which have been studied in many B-cell malignancies but are not yet approved in Canada.
The indolent non-Hodgkin’s lymphoma (iNHL) and chronic lymphocytic leukemia (CLL) landscape have been evolving over the past few years with many novel therapies being studied and becoming available. However, patients with RR iNHL, as well as patients using Bruton tyrosine kinase (BTK) and B-cell lymphoma-2 (BCL2) inhibitors for refractory CLL continue to have an unmet need for treatment. This article will focus on cellular therapy that will likely be available for use by Canadian clinicians in the near future to treat patients with iNHL and CLL.
References
Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. New England Journal of Medicine. 2017 Dec 28;377(26):2531-44. DOI: https://doi.org/10.1002/hon.2437_7
Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, Jäger U, Jaglowski S, Andreadis C, Westin JR, Fleury I. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. New England Journal of Medicine. 2019 Jan 3;380(1):45-56. DOI: https://doi.org/10.1056/NEJMoa1804980
Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, Verneris MR, Stefanski HE, Myers GD, Qayed M. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. New England Journal of Medicine. 2018 Feb 1;378(5):439-48. DOI: https://doi.org/10.1056/NEJMoa1709866
Wang M, Munoz J, Goy A, Locke FL, Jacobson CA, Hill BT, Timmerman JM, Holmes H, Jaglowski S, Flinn IW, McSweeney PA. KTE-X19 CAR T-cell therapy in relapsed or refractory mantle-cell lymphoma. New England journal of medicine. 2020 Apr 2;382(14):1331-42. DOI: https://doi.org/10.1056/NEJMoa1914347
Locke FL, Miklos DB, Jacobson CA, Perales MA, Kersten MJ, Oluwole OO, Ghobadi A, Rapoport AP, McGuirk J, Pagel JM, Muñoz J. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. New England Journal of Medicine. 2022 Feb 17;386(7):640-54. DOI: https://doi.org/10.1056/NEJMoa2116133
Kamdar M, Solomon SR, Arnason J, Johnston PB, Glass B, Bachanova V, Ibrahimi S, Mielke S, Mutsaers P, Hernandez-Ilizaliturri F, Izutsu K. 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 Jun 18;399(10343):2294-308. DOI: https://doi.org/10.1016/S0140-6736(22)00662-6
Morton LM, Wang SS, Devesa SS, Hartge P, Weisenburger DD, Linet MS. Lymphoma incidence patterns by WHO subtype in the United States, 1992-2001. Blood. 2006 Jan 1;107(1):265-76. DOI: https://doi.org/10.1182/blood-2005-06-2508
Bachy E, Seymour JF, Feugier P, Offner F, López-Guillermo A, Belada D, Xerri L, Catalano JV, Brice P, Lemonnier F, Martin A. Sustained progression-free survival benefit of rituximab maintenance in patients with follicular lymphoma: long-term results of the PRIMA study. Journal of Clinical Oncology. 2019 Nov 11;37(31):2815. DOI: https://doi.org/10.1200/JCO.19.01073
Jurinovic V, Kridel R, Staiger AM, Szczepanowski M, Horn H, Dreyling MH, Rosenwald A, Ott G, Klapper W, Zelenetz AD, Barr PM. Clinicogenetic risk models predict early progression of follicular lymphoma after first-line immunochemotherapy. Blood, The Journal of the American Society of Hematology. 2016 Aug 25;128(8):1112-20. DOI: https://doi.org/10.1182/blood-2016-05-717355
Jacobson CA, Chavez JC, Sehgal AR, William BM, Munoz J, Salles G, Munshi PN, Casulo C, Maloney DG, de Vos S, Reshef R. Axicabtagene ciloleucel in relapsed or refractory indolent non- Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial. The Lancet Oncology. 2022 Jan 1;23(1):91-103. DOI: https://doi.org/10.1016/S1470-2045(21)00591-X
Fowler NH, Dickinson M, Dreyling M, Martinez-Lopez J, Kolstad A, Butler J, Ghosh M, Popplewell L, Chavez JC, Bachy E, Kato K. Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial. Nature medicine. 2022 Feb;28(2):325-32.
Jacobson CA, Chavez JC, Sehgal A, William BM, Munoz J, Salles GA, Casulo C, Munshi PN, Maloney DG, De Vos S, Reshef R. Outcomes in ZUMA-5 with axicabtagene ciloleucel (axi-cel) in patients (pts) with relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL) who had the high-risk feature of progression within 24 months from initiation of first anti-CD20–containing chemoimmunotherapy (POD24).
Thieblemont C, Dickinson M, Martinez-Lopez J, Kolstad A, Butler JP, Ghosh M, Popplewell LL, Chavez JC, Bachy E, Kato K, Harigae H. Efficacy of tisagenlecleucel in adult patients (Pts) with high-risk relapsed/refractory follicular lymphoma (r/r FL): subgroup analysis of the phase II Elara study. Blood. 2021 Nov 23;138:131.
Abramson JS, Palomba ML, Gordon LI, Lunning MA, Wang M, Arnason J, Mehta A, Purev E, Maloney DG, Andreadis C, Sehgal A. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. The Lancet. 2020 Sep 19;396(10254):839-52. DOI: https://doi.org/10.1016/S0140-6736(20)31366-0
Budde LE, Bartlett NL. Single-agent mosunetuzumab shows durable complete responses in patients with relapsed or refractory B-cell lymphomas: phase I dose-escalation study. American Society of Clinical Oncology.
Budde LE, Sehn LH, Matasar M, Schuster SJ, Assouline S, Giri P, Kuruvilla J, Canales M, Dietrich S, Fay K, Ku M. Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. The Lancet Oncology. 2022 Aug 1;23(8):1055-65. DOI: https://doi.org/10.1016/S1470-2045(22)00335-7
Hutchings M, Morschhauser F, Iacoboni G, Carlo-Stella C, Offner FC, Sureda A, Salles G, Martínez- Lopez J, Crump M, Thomas DN, Morcos PN. 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 Jun 6;39(18):1959. DOI: https://doi.org/10.1200/JCO.20.03175
Hutchings M, Mous R, Clausen MR, Johnson P, Linton KM, Chamuleau ME, Lewis DJ, Balari AS, Cunningham D, Oliveri RS, Elliott B. 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 Sep 25;398(10306):1157-69. DOI: https://doi.org/10.1016/S0140-6736(21)00889-8
Bannerji R, Arnason JE, Advani RH, Brown JR, Allan JN, Ansell SM, Barnes JA, O’Brien SM, Chávez JC, Duell J, Rosenwald A. 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. The Lancet Haematology. 2022 May 1;9(5):e327-39. DOI: https://doi.org/10.1016/S2352-3026(22)00072-2
Siddiqi T, Soumerai JD, Dorritie KA, Stephens DM, Riedell PA, Arnason J, Kipps TJ, Gillenwater HH, Gong L, Yang L, Ogasawara K. Phase 1 TRANSCEND CLL 004 study of lisocabtagene maraleucel in patients with relapsed/refractory CLL or SLL. Blood. 2022 Mar 24;139(12):1794-806. DOI: https://doi.org/10.1182/blood.2021011895
Turtle CJ, Hay KA, Hanafi LA, Li D, Cherian S, Chen X, Wood B, Lozanski A, Byrd JC, Heimfeld S, Riddell SR. Durable molecular remissions in chronic lymphocytic leukemia treated with CD19- specific chimeric antigen receptor–modified T cells after failure of ibrutinib. Journal of Clinical Oncology. 2017 Sep 9;35(26):3010. DOI: https://doi.org/10.1200/JCO.2017.72.8519
Gauthier J, Hirayama AV, Purushe J, Hay KA, Lymp J, Li DH, Yeung CC, Sheih A, Pender BS, Hawkins RM, Vakil A. Feasibility and efficacy of CD19-targeted CAR T cells with concurrent ibrutinib for CLL after ibrutinib failure. Blood, The Journal of the American Society of Hematology. 2020 May 7;135(19):1650-60. DOI: https://doi.org/10.1182/blood.2019002936
Porter DL, Hwang WT, Frey NV, Lacey SF, Shaw PA, Loren AW, Bagg A, Marcucci KT, Shen A, Gonzalez V, Ambrose D. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Science translational medicine. 2015 Sep 2;7(303):303ra139. DOI: https://doi.org/10.1126/scitranslmed.aac5415
Kater AP, Christensen JH, Bentzen HH, Niemann CU, Hutchings M, Chen J, Rios M, Palenski T, Li T, Mato AR. Subcutaneous epcoritamab in patients with relapsed/refractory chronic lymphocytic leukemia: preliminary results from the Epcore CLL-1 trial. Blood. 2021 Nov 23;138:2627. DOI: https://doi.org/10.1182/blood-2021-146563
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Canadian Hematology Today
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
