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Acalabrutinib in ibrutinib-intolerant R/R CLL patients
Funding
KAR is a scholar in clinical research of and received grant support from the Leukemia & Lymphoma Society. This grant provides salary support for clinical research and for writing and other study activities. The study was funded by Acerta Pharma (South San Francisco, CA, USA) a member of the AstraZeneca Group. Acerta Pharma provided the study drug. Medical writ- ing assistance, funded by Acerta Pharma, was provided by Tracy Diaz, PhD, and Cindy Gobbel, PhD, of Peloton Advantage, LLC, an OPEN Health company.
Data-sharing
Acerta Pharma, a member of the AstraZeneca Group, is commit- ted to data transparency and will consider data-sharing requests on a case-by-case basis. Any requests for de-identified patients’ data can be submitted to Acerta Pharma 3 months post-publication and ending 5 years following article publication with the intent-to- achieve aims of the original proposal. In addition, Acerta Pharma will provide the study protocol, statistical analysis plan, and informed consent form, as well as post results on clinicaltrials.gov, as required.
References
1. Pal Singh S, Dammeijer F, Hendriks RW. Role of Bruton's tyrosine kinase in B cells and malignancies. Mol Cancer. 2018;17(1):57.
2. Herman SE, Gordon AL, Hertlein E, et al. Bruton tyrosine kinase represents a promis- ing therapeutic target for treatment of chronic lymphocytic leukemia and is effec- tively targeted by PCI-32765. Blood. 2011;117(23):6287-6296.
3.Woyach JA, Bojnik E, Ruppert AS, et al. Bruton's tyrosine kinase (BTK) function is important to the development and expan- sion of chronic lymphocytic leukemia (CLL). Blood. 2014;123(8):1207-1213.
4. Herman SEM, Montraveta A, Niemann CU, et al. The Bruton tyrosine kinase (BTK) inhibitor acalabrutinib demonstrates potent on-target effects and efficacy in two mouse models of chronic lymphocytic leukemia. Clin Cancer Res. 2017;23(11): 2831-2841.
5.Byrd JC, Furman RR, Coutre SE, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369(1):32-42.
6. Mato AR, Nabhan C, Thompson MC, et al. Toxicities and outcomes of 616 ibrutinib- treated patients in the United States: a real- world analysis. Haematologica. 2018;103(5): 874-879.
7. Bose P, Gandhi VV, Keating MJ. Pharmacokinetic and pharmacodynamic evaluation of ibrutinib for the treatment of chronic lymphocytic leukemia: rationale for lower doses. Expert Opin Drug Metab Toxicol. 2016;12(11):1381-1392.
8. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma version 2.2021. December 3, 2020. Available from: https://www.nccn.org/ profession- als/physician_gls/default.aspx. Accessed December 21, 2020.
9.O'Brien S, Furman RR, Coutre S, et al. Single-agent ibrutinib in treatment-naive and relapsed/refractory chronic lymphocytic leukemia: a 5-year experience. Blood. 2018;131(17):1910-1919.
10. Calquence approved in the US for adult patients with chronic lymphocytic
leukaemia [press release]. 2019. Available from: https://www.astrazeneca.com/con- tent/astraz/media-centre/press- releases/2019/calquence-approved-in-the- us-for-adult-patients-with-chronic-lympho- cytic-leukaemia-21112019.html. Accessed December 21, 2020.
11. Byrd JC, Harrington B, O'Brien S, et al. Acalabrutinib (ACP-196) in relapsed chronic lymphocytic leukemia. N Engl J Med. 2016;374(4):323-332.
12. Bye AP, Unsworth AJ, Desborough MJ, et al. Severe platelet dysfunction in NHL patients receiving ibrutinib is absent in patients receiving acalabrutinib. Blood Adv. 2017;1 (26):2610-2623.
13.Barf T, Covey T, Izumi R, et al. Acalabrutinib (ACP-196): a covalent bruton tyrosine kinase inhibitor with a differentiat- ed selectivity and in vivo potency profile. J Pharmacol Exp Ther. 2017;363(2):240-252.
14. Byrd JC, Brown JR, O'Brien S, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014;371(3):213-223.
15. Ghia P, Pluta A, Wach M, et al. ASCEND: phase III, randomized trial of acalabrutinib versus idelalisib plus rituximab or ben- damustine plus rituximab in relapsed or refractory chronic lymphocytic leukemia. J Clin Oncol. 2020;38(25):2849-2861.
16. Awan FT, Schuh A, Brown JR, et al. Acalabrutinib monotherapy in patients with chronic lymphocytic leukemia who are intolerant to ibrutinib. Blood Adv. 2019;3(9): 1553-1562.
17. Hallek M, Cheson BD, Catovsky D, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008;111(12): 5446-5456.
18.Woyach JA, Ruppert AS, Guinn D, et al. BTK(C481S)-mediated resistance to ibruti- nib in chronic lymphocytic leukemia. J Clin Oncol. 2017;35(13):1437-1443.
19. Jones D, Woyach JA, Zhao W, et al. PLCG2 C2 domain mutations co-occur with BTK and PLCG2 resistance mutations in chronic lymphocytic leukemia undergoing ibrutinib treatment. Leukemia. 2017;31(7):1645-1647.
20. Byrd JC, Wierda WG, Schuh A, et al.
Acalabrutinib monotherapy in patients with relapsed/refractory chronic lymphocytic leukemia: updated phase 2 results. Blood. 2020;135(15):1204-1213.
21.Woyach JA, Furman RR, Liu TM, et al. Resistance mechanisms for the Bruton's tyrosine kinase inhibitor ibrutinib. N Engl J Med. 2014;370(24):2286-2294.
22. Woyach J, Huang Y, Rogers K, et al. Resistance to acalabrutinib in CLL is mediat- ed primarily by BTK mutations. Blood. 2019;134(Suppl 1):504.
23. Albitar A, Ma W, DeDios I, et al. Using high- sensitivity sequencing for the detection of mutations in BTK and PLCgamma2 genes in cellular and cell-free DNA and correlation with progression in patients treated with BTK inhibitors. Oncotarget. 2017;8(11): 17936-17944.
24. Liu TM, Woyach JA, Zhong Y, et al. Hypermorphic mutation of phospholipase C, gamma2 acquired in ibrutinib-resistant CLL confers BTK independency upon B- cell receptor activation. Blood. 2015;126(1): 61-68.
25. O'Brien S, Furman RR, Coutre SE, et al. Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial. Lancet Oncol. 2014;15(1):48-58.
26. Series J, Garcia C, Levade M, et al. Differences and similarities in the effects of ibrutinib and acalabrutinib on platelet func- tions. Haematologica. 2019;104(11):2292- 2299.
27. Mato AR, Nabhan C, Barr PM, et al. Outcomes of CLL patients treated with sequential kinase inhibitor therapy: a real world experience. Blood. 2016;128(18): 2199-2205.
28. Mato AR, Schuster SJ, Lamanna N, et al. A phase 2 study to assess the safety and effica- cy of umbralisib (TGR-1202) in patients with chronic lymphocytic leukemia (CLL) who are intolerant to prior BTK or PI3Kδ inhibitor therapy. Hematol Oncol. 2019;37(s2):88-89.
29. Ghia P, Pluta A, Wach M, et al. ASCEND: Phase III, randomized trial of acalabrutinib versus idelalisib plus rituximab or ben- damustine plus rituximab in relapsed or refractory chronic lymphocytic leukemia. J Clin Oncol. 2020;38(25):2849-2861.
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