Bruton Tyrosine Kinase Inhibitors for B-Cell Malignancies
Abstract
Over the last 10 years, Bruton Tyrosine kinase inhibitors (BTKi) have been a significant breakthrough for the treatment of B-cell malignancies, especially in chronic lymphocytic leukemia (CLL). Since the initial publication of the activity of ibrutinib in 2013, many publications have highlighted the improved outcomes for patients with B-cell malignancies owing to the use of ibrutinib and other BTKi. BTKi monotherapy has been standard of care for many years and more recently, combination therapies that include targeted therapy or chemotherapy are being studied.
References
Advani RH, Buggy JJ, Sharman JP, Smith SM, Boyd TE, Grant B, et al. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol. 2013;31(1):88-94.
Byrd JC, Hillmen P, O’Brien S, Barrientos JC, Reddy NM, Coutre S, et al. Long-term follow-up of the RESONATE phase 3 trial of ibrutinib vs ofatumumab. Blood. 2019;133(19):2031-2042.
Alu A, Lei H, Han X, Wei Y, Wei X. BTK inhibitors in the treatment of hematological malignancies and inflammatory diseases: mechanisms and clinical studies. J Hematol Oncol. 2022;15(1):138. doi: 10.1186/s13045-022-01353-w.
Mato AR, Woyach JA, Brown JR, Ghia P, Patel K, Eyre TA, et al. Pirtobrutinib after a covalent BTK Inhibitor in chronic lymphocytic leukemia. N Engl J Med. 2023;389(1):33-44.
Owen C, Banerji V, Johnson N, Gerrie A, Aw A, Chen C, et al. Canadian evidence-based guideline for frontline treatment of chronic lymphocytic leukemia: 2022 update. Leuk Res. 2023;125:107016. doi: 10.1016/j.leukres.2023.107016. Epub 2023 Jan 5. Erratum in: Leuk Res. 2023;128:107073.
Shanafelt TD, Wang XV, Kay NE, Hanson CA, O’Brien S, Barrientos J, et al. Ibrutinib-rituximab or chemoimmunotherapy for chronic lymphocytic leukemia. N Engl J Med. 2019;381(5):432-443.
Hillmen P, Pitchford A, Bloor A, Broom A, Young M, Kennedy B, et al. Ibrutinib and rituximab versus fludarabine, cyclophosphamide, and rituximab for patients with previously untreated chronic lymphocytic leukaemia (FLAIR): interim analysis of a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023;24(5):535-552.
Burger JA, Tedeschi A, Barr PM, Robak T, Owen C, Ghia P, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015;373(25):2425-2437.
Moreno C, Greil R, Demirkan F, Tedeschi A, Anz B, Larratt L, et al. Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20(1):43-56.
Woyach JA, Ruppert AS, Heerema NA, Zhao W, Booth AM, Ding W, et al. Ibrutinib regimens versus chemoimmunotherapy in older patients with untreated CLL. N Engl J Med. 2018;379(26):2517-2528.
Sharman JP, Egyed M, Jurczak W, Skarbnik A, Pagel JM, Flinn IW, et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. Lancet. 2020;395(10232):1278-1291.
Tam CS, Brown JR, Kahl BS, Ghia P, Giannopoulos K, Jurczak W, et al. Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial. Lancet Oncol. 2022;23(8):1031-1043.
Byrd JC, Brown JR, O’Brien S, Barrientos JC, Kay NE, Reddy NM, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014;371(3):213-223.
Munir T, Brown JR, O’Brien S, Barrientos JC, Barr PM, Reddy NM, et al. Final analysis from RESONATE: up to six years of follow-up on ibrutinib in patients with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma. Am J Hematol. 2019;94(12):1353-1363.
Ghia P, Pluta A, Wach M, Lysak D, Kozak T, Simkovic M, et al. ASCEND: phase III, randomized trial of acalabrutinib versus idelalisib plus rituximab or bendamustine plus rituximab in relapsed or refractory chronic lymphocytic leukemia. J Clin Oncol. 2020;38(25):2849-2861.
Ghia P, Pluta A, Wach M, Lysak D, Simkovic M, Kriachok I, et al. Acalabrutinib versus investigator’s choice in relapsed/refractory chronic lymphocytic leukemia: final ASCEND trial results. Hemasphere. 2022;6(12):e801.
Byrd JC, Hillmen P, Ghia P, Kater AP, Chanan-Khan A, Furman RR, et al. Acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia: results of the first randomized phase III trial. J Clin Oncol. 2021;39(31):3441-3452.
Brown JR, Eichhorst B, Hillmen P, Jurczak W, Kazmierczak M, Lamanna N, et al. Zanubrutinib or Ibrutinib in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2023;388(4):319-332.
Roeker LE, DerSarkissian M, Ryan K, Chen Y, Duh MS, Wahlstrom SK, et al. Real-world comparative effectiveness of acalabrutinib and ibrutinib in patients with chronic lymphocytic leukemia. Blood Adv. 2023;7(16):4291-4301.
Shadman M, Manzoor BS, Sail K, Tuncer HH, Allan JN, Ujjani C, et al. Treatment discontinuation patterns for patients with chronic lymphocytic leukemia in real-world settings: results from a multi-center international study. Clin Lymphoma Myeloma Leuk. 2023;23(7):515-526.
Wang ML, Jurczak W, Jerkeman M, Trotman J, Zinzani PL, Belada D, et al. Ibrutinib plus bendamustine and rituximab in untreated mantle-cell lymphoma. N Engl J Med. 2022;386(26):2482-2494.
Dreyling M, Jurczak W, Jerkeman M, Silva RS, Rusconi C, Trneny M, et al. Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study. Lancet. 2016;387(10020):770-778.
Dimopoulos MA, Tedeschi A, Trotman J, Garcia-Sanz R, Macdonald D, Leblond V, et al. Phase 3 trial of ibrutinib plus rituximab in Waldenstrom’s macroglobulinemia. N Engl J Med. 2018;378(25):2399-2410.
Tam CS, Opat S, D’Sa S, Jurczak W, Lee HP, Cull G, et al. A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenstrom macroglobulinemia: the ASPEN study. Blood. 2020;136(18):2038-2050.
Wang ML, Jain P, Zhao S, Lee HJ, Nastoupil L, Fayad L, et al. Ibrutinib-rituximab followed by R-HCVAD as frontline treatment for young patients (=65 years) with mantle cell lymphoma (WINDOW-1): a single-arm, phase 2 trial. Lancet Oncol. 2022;23(3):406-415.
Wang M, Rule S, Zinzani PL, Goy A, Casasnovas O, Smith SD, et al. Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. Lancet. 2018;391(10121):659-667.
Tam CS, Opat S, Simpson D, Cull G, Munoz J, Phillips TJ, et al. Zanubrutinib for the treatment of relapsed or refractory mantle cell lymphoma. Blood Adv. 2021;5(12):2577-2585.
Owen RG, McCarthy H, Rule S, D’Sa S, Thomas SK, Tournilhac O, et al. Acalabrutinib monotherapy in patients with Waldenstrom macroglobulinemia: a single-arm, multicentre, phase 2 study. Lancet Haematol. 2020;7(2):e112-e121.
Wilson WH, Young RM, Schmitz R, Yang Y, Pittaluga S, Wright G, et al. Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma. Nat Med. 2015;21(8):922-926.
Noy A, de Vos S, Thieblemont C, Martin P, Flowers CR, Morschhauser F, et al. Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma. Blood. 2017;129(16):2224-2232.
Opat S, Tedeschi A, Linton K, McKay P, Hu B, Chan H, et al. The MAGNOLIA trial: zanubrutinib, a next-generation Bruton tyrosine kinase inhibitor, demonstrates safety and efficacy in relapsed/refractory marginal zone lymphoma. Clin Cancer Res. 2021;27(23):6323-6332.
Soussain C, Choquet S, Blonski M, Leclercq D, Houillier C, Rezai K, et al. Ibrutinib monotherapy for relapse or refractory primary CNS lymphoma and primary vitreoretinal lymphoma: final analysis of the phase II ‘proof-of-concept’ iLOC study by the Lymphoma study association (LYSA) and the French oculo-cerebral lymphoma (LOC) network. Eur J Cancer. 2019;117:121-130.
Fowler NH, Nastoupil L, De Vos S, Knapp M, Flinn IW, Chen R, et al. The combination of ibrutinib and rituximab demonstrates activity in first-line follicular lymphoma. Br J Haematol. 2020;189(4):650-660.
Zinzani PL, Mayer J, Flowers CR, Bijou F, De Oliveira AC, Song Y, et al. ROSEWOOD: a phase II randomized study of zanubrutinib plus obinutuzumab versus obinutuzumab monotherapy in patients with relapsed or refractory follicular lymphoma. J Clin Oncol. 2023;41(33):5107-5117. doi:10.1200/JCO.23.00775
Estupinan HY, Berglof A, Zain R, Smith CIE. Comparative analysis of btk inhibitors and mechanisms underlying adverse effects. Front Cell Dev Biol. 2021;9:630942.
Benjamin EJ, Wolf PA, D’Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation. 1998;98(10):946-952.
Gomez EB, Ebata K, Randeria HS, Rosendahl MS, Cedervall EP, Morales TH, et al. Preclinical characterization of pirtobrutinib, a highly selective, noncovalent (reversible) BTK inhibitor. Blood. 2023;142(1):62-72.
Mato AR, Shah NN, Jurczak W, Cheah CY, Pagel JM, Woyach JA, et al. Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study. Lancet. 2021;397(10277):892-901.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Canadian Hematology Today
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
