Cellular therapy in CLL/iNHL: Therapeutic agents in the pipeline

Authors

  • Christopher Lemieux, MD, FRCPC CHU de Québec-Université Laval

DOI:

https://doi.org/10.58931/cht.2023.2232

Abstract

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.

Author Biography

Christopher Lemieux, MD, FRCPC, CHU de Québec-Université Laval

Dr. Christopher Lemieux is a Hematologist at the CHU de Québec-Université Laval. He completed specialized training in transplantation and cell therapy at Stanford University in California, for which he received the Detweiler scholarship from the Royal College of Physicians and Surgeons of Canada and the Stephen Couban prize of the Canadian Hematology Society. With this experience, he is currently director of the CAR-T program at the CHU de Québec-Université Laval and is a member of the immunocellular therapy network in Québec. He is a Clinical Associate Professor of Medicine and director of the Hematology fellowship program at Université Laval.

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

2023-06-07

How to Cite

1.
Lemieux C. Cellular therapy in CLL/iNHL: Therapeutic agents in the pipeline. Can Hematol Today [Internet]. 2023 Jun. 7 [cited 2024 Apr. 15];2(2):12–14. Available from: https://canadianhematologytoday.com/article/view/2-2-lemieux

Issue

Section

Articles

Most read articles by the same author(s)