Keywords
Zanubrutinib, BTK, BTK inhibitors, mantle cell lymphoma, chronic lymphocytic leukemia.
How to Cite
Cugliari, M. S. (2021). Second generation BTK inhibitors: zanubrutinib New therapeutic agent for B- lymphoproliferative disorders. Journal of Hematology, 25(2), 68–74. Retrieved from https://revistahematologia.com.ar/index.php/Revista/article/view/383
Abstract
Bruton's tyrosine kinase is a tyrosine kinase expressed in the entire hematopoietic lineage, except for T cell progenitors, and plays an essential role in the BCR pathway. Inhibition of BTK has proven to be an effective strategy in some lymphomas and chronic lymphocytic leukemia. Ibrutinib and acalabrutinib are BTK inhibitors approved in Argentina.
Zanubrutinib is a more specific iBTK, which would explain some differences with those previously developed. Many studies with zanubrutinib in different B-lymphoproliferative syndromes are in development or with different follow-up and it demonstrate a more selective inhibition with more complete and sustained occupation of BTK, which would result in greater benefits in efficacy and safety.
References
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8- ANMAT Disposición No 3549 (22/05/2020) y 5732 (17/07/2019).
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13- Sawalha Y. , Bond D., Alinari L. Evaluating the Therapeutic Potential of Zanubrutinib in the Treatment of R/R Mantle Cell Lymphoma: Evidence to Date. OncoTargets Ther 2020; 13: 6573-6581.
14- Tam CS, Opat S, Zhu J. y col. PS1159 pooled analysis of safety data from monotherapy studies of the BTK inhibitor, zanubrutinib (BGB-3111), in B-cell malignancies. HemaSphere. 2019;3(S1):526.
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17- Song Y. y col, (EP789) Zanubrutinib in patients with R/R MCL: long term efficacy and safety results from a phase 2 study. 2021 European Hematology Association (EHA2021) Congress in June 2021. Available at EHA Open Access Library.
18- Dreyling M, Tam C, Wang M y col., A Phase III study of zanubrutinib plus rituximab versus bendamustine plus rituximab in transplant-ineligible, untreated mantle cell lymphoma. FutureOncol (2021)17(3),255–262.
19- Soumerai J y col. (S214) TOLERABILITY AND EFFICACY OF THE COMBINATION OF PI3KΔ INHIBITOR ZANDELISIB (ME-401) AND BTK INHIBITOR ZANUBRUTINIB IN PATIENTS WITH R/R B-CELL MALIGNANCIES: INITIAL RESULTS. 2021 European Hematology Association (EHA2021) Congress in June 2021. Available at EHA Open Access Library.
20- Opat S, y col (EP783) PHASE 2 STUDY OF ZANUBRUTINIB IN PATIENTS WITH R/R MARGINAL ZONE LYMPHOMA (MAGNOLIA STUDY). 2021 European Hematology Association (EHA 2021) Congress in June 2021. Available at EHA Open Access Library.
21- Xu W, Yang S, Zhou K, y col. Treatment of R/R SLL/CLL with the BTK inhibitor zanubrutinib: phase 2, single-arm, multicenter study. J Hematol Oncol. 2020;13(1):48.
22- Tam CS, Robak T, Ghia P, et al. Efficacy and safety of zanubrutinib in patients with treatment-naive CLL or SLL with del(17p): initial results from arm C of the Sequoia (BGB-3111-304) trial.
23- https://clinicaltrials.gov/ct2/show/NCT03824483
24- https://clinicaltrials.gov/ct2/show/NCT04515238
25- https://clinicaltrials.gov/ct2/show/NCT04458610
26- Shadman M, y col (EP642) PRELIMINARY RESULTS OF THE PHASE 2 STUDY OF ZANUBRUTINIB IN PATIENTS WITH PREVIOUSLY TREATED B-CELL MALIGNANCIES INTOLERANT TO IBRUTINIB and/or acalabrutinib. 2021 European Hematology Association (EHA 2021) Congress in June 2021. Available at EHA Open Access Library.
27- XU W. y col (EP639) ZANUBRUTINIB MONOTHERAPY IN PATIENTS WITH R/R CLL: 34-MONTH FOLLOW-UP RESULTS. 2021 European Hematology Association (EHA2021) Congress in June 2021. Available at EHA Open Access Library.
28- https://www.businesswire.com/news/home/20210729006225/en/BeiGene-Announces-Positive-Topline-Results-from-Phase-3-SEQUOIA-Trial-Comparing-BRUKINSA%C2%AE-Zanubrutinib-to-Bendamustine-Plus-Rituximab-in-Patients-with-Treatment-Na%C3%AFve-Chronic-Lymphocytic-Leukemia.
29- Tam CS, Robak T, Ghia P y col. Zanubrutinib monotherapy for patients with treatment naïve CLL and 17p deletion. Haematologica. 2020 Oct13; Online ahead of print.
30- Brown JR, Robak T, Ghia P y col. Efficacy and safety of zanubrutinib in patients with Treatment-Naïve CLL/SLL with del (17p): follow-up results from arm C of the SEQUOIA (BGB-3111- 304) trial. Blood. 2020;136(Supplement 1):11–12.
31- Tam CS, Flinn IW, Tedeschi A, y col. Zanubrutinib in combination with venetoclax for patients with treatment-naïve CLL/SLL and del(17p): arm D of the SEQUOIA (BGB-3111-304) trial. Blood. 2020;136(Supplement 1):24–25.
32- Hillmen P, Eichhorst B, Brown J y col. (LB1900) FIRST INTERIM ANALYSIS OF ALPINE STUDY: RESULTS OF A PHASE 3 RANDOMIZED STUDY OF ZANUBRUTINIB VS IBRUTINIB IN PATIENTS WITH R/R CLL/SLL. 2021 European Hematology Association (EHA2021) Congress in June 2021. Available at EHA Open Access Library.
33- Tam C, Opat S, D´Sa S y col. A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström Macroglobulinemia: the ASPEN study. Blood 2020; 136 (18): 2038–2050.
34- Castillo, J., y col. (EP805) EFFICACY AND SAFETY OF ZANUBRUTINIB VERSUS RITUXIMAB-BASED CHEMOIMMUNOTHERAPY IN WALDENSTRÖM MACROGLOBULINEMIA: MATCHING-ADJUSTED INDIRECT COMPARISONS. 2021 European Hematology Association (EHA2021) Congress in June 2021. Available at EHA Open Access Library.
35- NCCN CLL/SLL. Version 2.2021. https://www.nccn.org/professionals/physician_gls/pdf/cll.pdf. Published Dec 3, 2020. Accessed Jan 8, 2021.
36- Stephens D. Second-Generation BTK Inhibitors: Simply the Best Treatments for CLL?. Publicado en ascopubs.org/journal/jco on July 26, 2021.
2- Administración Nacional de Medicamentos, Alimentos y Tecnología Médica (ANMAT) Disposición No 9440 (11/11/2015) y No 12655 (13/12/2017).
3- Mato AR, Nabhan C, Thompson MC, y col. Toxicities and outcomes of 616 ibrutinib-treated patients in the US: a real-world analysis. Haematologica. 2018;103(5):874–879.
4- Stephens DM, Byrd JC. How I manage ibrutinib intolerance and complications in patients with CLL. Blood. 2019;133(12):1298–1307.
5- Sharman JP, Egyed M, Jurczak W y col. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzumab for treatment-naive CLL (ELEVATE TN): a randomized, controlled, phase 3 trial. Lancet. 2020 Apr 18;395(10232):1278-1291.
6- Ghia P, Pluta A, Wach M y col. ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in R/R CLL. J Clin Oncol 2020; 38:25, 2849-2861
7- Wang M, Rule S, Zinzani PL, et al. Acalabrutinib in R/R mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. Lancet. 2018;391(10121):659-667.
8- ANMAT Disposición No 3549 (22/05/2020) y 5732 (17/07/2019).
9- Dobie G, Kurini F, Omar M y col., Ibrutinib, but not zanubrutinib, induces platelet receptor shedding of GPIb-IX-V complex and integrin αIIbβ3 in mice and humans. Blood Adv 2019; 3 (24): 4298–4311.
10- Flinsenberg TWH, Tromedjo CC, Hu N. y col., Differential effects of BTK inhibitors ibrutinib and zanubrutinib on NK-cell effector function in patients with mantle cell lymphoma. Haematologica 2020;105(2):e76-e79.
11- Tam CS, Trotman J, Opat S. y col. Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood. 2019;134(11):851–859.
12- Song Y., Zhou K., Zou D. y col., Treatment of Patients with R/R Mantle–Cell Lymphoma with Zanubrutinib, a Selective Inhibitor of Bruton's Tyrosine Kinase. Clin Cancer Res 2020;26:4216–24.
13- Sawalha Y. , Bond D., Alinari L. Evaluating the Therapeutic Potential of Zanubrutinib in the Treatment of R/R Mantle Cell Lymphoma: Evidence to Date. OncoTargets Ther 2020; 13: 6573-6581.
14- Tam CS, Opat S, Zhu J. y col. PS1159 pooled analysis of safety data from monotherapy studies of the BTK inhibitor, zanubrutinib (BGB-3111), in B-cell malignancies. HemaSphere. 2019;3(S1):526.
15- Weaver, A.N. and Jimeno, A. Zanubrutinib: a new BTK inhibitor for treatment of R/R mantle cell lymphoma. Drugs Today 2020, 56(8): 531.
16- Tam C, Opat S, Simpson D y col. Zanubrutinib for the treatment of R/R mantle cell lymphoma. Blood Adv 2021; 5 (12): 2577–2585.
17- Song Y. y col, (EP789) Zanubrutinib in patients with R/R MCL: long term efficacy and safety results from a phase 2 study. 2021 European Hematology Association (EHA2021) Congress in June 2021. Available at EHA Open Access Library.
18- Dreyling M, Tam C, Wang M y col., A Phase III study of zanubrutinib plus rituximab versus bendamustine plus rituximab in transplant-ineligible, untreated mantle cell lymphoma. FutureOncol (2021)17(3),255–262.
19- Soumerai J y col. (S214) TOLERABILITY AND EFFICACY OF THE COMBINATION OF PI3KΔ INHIBITOR ZANDELISIB (ME-401) AND BTK INHIBITOR ZANUBRUTINIB IN PATIENTS WITH R/R B-CELL MALIGNANCIES: INITIAL RESULTS. 2021 European Hematology Association (EHA2021) Congress in June 2021. Available at EHA Open Access Library.
20- Opat S, y col (EP783) PHASE 2 STUDY OF ZANUBRUTINIB IN PATIENTS WITH R/R MARGINAL ZONE LYMPHOMA (MAGNOLIA STUDY). 2021 European Hematology Association (EHA 2021) Congress in June 2021. Available at EHA Open Access Library.
21- Xu W, Yang S, Zhou K, y col. Treatment of R/R SLL/CLL with the BTK inhibitor zanubrutinib: phase 2, single-arm, multicenter study. J Hematol Oncol. 2020;13(1):48.
22- Tam CS, Robak T, Ghia P, et al. Efficacy and safety of zanubrutinib in patients with treatment-naive CLL or SLL with del(17p): initial results from arm C of the Sequoia (BGB-3111-304) trial.
23- https://clinicaltrials.gov/ct2/show/NCT03824483
24- https://clinicaltrials.gov/ct2/show/NCT04515238
25- https://clinicaltrials.gov/ct2/show/NCT04458610
26- Shadman M, y col (EP642) PRELIMINARY RESULTS OF THE PHASE 2 STUDY OF ZANUBRUTINIB IN PATIENTS WITH PREVIOUSLY TREATED B-CELL MALIGNANCIES INTOLERANT TO IBRUTINIB and/or acalabrutinib. 2021 European Hematology Association (EHA 2021) Congress in June 2021. Available at EHA Open Access Library.
27- XU W. y col (EP639) ZANUBRUTINIB MONOTHERAPY IN PATIENTS WITH R/R CLL: 34-MONTH FOLLOW-UP RESULTS. 2021 European Hematology Association (EHA2021) Congress in June 2021. Available at EHA Open Access Library.
28- https://www.businesswire.com/news/home/20210729006225/en/BeiGene-Announces-Positive-Topline-Results-from-Phase-3-SEQUOIA-Trial-Comparing-BRUKINSA%C2%AE-Zanubrutinib-to-Bendamustine-Plus-Rituximab-in-Patients-with-Treatment-Na%C3%AFve-Chronic-Lymphocytic-Leukemia.
29- Tam CS, Robak T, Ghia P y col. Zanubrutinib monotherapy for patients with treatment naïve CLL and 17p deletion. Haematologica. 2020 Oct13; Online ahead of print.
30- Brown JR, Robak T, Ghia P y col. Efficacy and safety of zanubrutinib in patients with Treatment-Naïve CLL/SLL with del (17p): follow-up results from arm C of the SEQUOIA (BGB-3111- 304) trial. Blood. 2020;136(Supplement 1):11–12.
31- Tam CS, Flinn IW, Tedeschi A, y col. Zanubrutinib in combination with venetoclax for patients with treatment-naïve CLL/SLL and del(17p): arm D of the SEQUOIA (BGB-3111-304) trial. Blood. 2020;136(Supplement 1):24–25.
32- Hillmen P, Eichhorst B, Brown J y col. (LB1900) FIRST INTERIM ANALYSIS OF ALPINE STUDY: RESULTS OF A PHASE 3 RANDOMIZED STUDY OF ZANUBRUTINIB VS IBRUTINIB IN PATIENTS WITH R/R CLL/SLL. 2021 European Hematology Association (EHA2021) Congress in June 2021. Available at EHA Open Access Library.
33- Tam C, Opat S, D´Sa S y col. A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström Macroglobulinemia: the ASPEN study. Blood 2020; 136 (18): 2038–2050.
34- Castillo, J., y col. (EP805) EFFICACY AND SAFETY OF ZANUBRUTINIB VERSUS RITUXIMAB-BASED CHEMOIMMUNOTHERAPY IN WALDENSTRÖM MACROGLOBULINEMIA: MATCHING-ADJUSTED INDIRECT COMPARISONS. 2021 European Hematology Association (EHA2021) Congress in June 2021. Available at EHA Open Access Library.
35- NCCN CLL/SLL. Version 2.2021. https://www.nccn.org/professionals/physician_gls/pdf/cll.pdf. Published Dec 3, 2020. Accessed Jan 8, 2021.
36- Stephens D. Second-Generation BTK Inhibitors: Simply the Best Treatments for CLL?. Publicado en ascopubs.org/journal/jco on July 26, 2021.
All material published in the journal HEMATOLOGÍA (electronic and print version) is transferred to the Argentinean Society of Hematology. In accordance with the copyright Act (Act 11 723), a copyright transfer form will be sent to the authors of approved works, which has to be signed by all the authors before its publication. Authors should keep a copy of the original since the journal is not responsible for damages or losses of the material that was submitted. Authors should send an electronic version to the email: revista@sah.org.ar
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