Bruton's tyrosine kinase (BTK) inhibitors in clinical trials

Current Hematologic Malignancy Reports

Volumn 9, Issue 1, 2014, Pages 44-49

  Burger, Jan A ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

B cell receptor; BCR; BTK; CC 292; Chronic lymphocytic leukemia; CLL; ibrutinib; Microenvironment

Indexed keywords

2 CYANO N (2,5 DIBROMOPHENYL) 3 HYDROXYCROTONAMIDE; B LYMPHOCYTE RECEPTOR; BRUTON TYROSINE KINASE; BRUTON TYROSINE KINASE INHIBITOR; CC 292; IBRUTINIB; ONO 4059; RITUXIMAB; UNCLASSIFIED DRUG;

B LYMPHOCYTE; CANCER INHIBITION; CANCER SURVIVAL; CHRONIC LYMPHATIC LEUKEMIA; CLINICAL TRIAL (TOPIC); DIARRHEA; DRUG ERUPTION; DRUG INDICATION; DRUG TOLERABILITY; DYSPNEA; EDEMA; ENZYME ACTIVATION; FATIGUE; GENE TARGETING; HUMAN; IC 50; IMMUNORECEPTOR TYROSINE BASED ACTIVATION MOTIF; LARGE CELL LYMPHOMA; LEUKEMIA RELAPSE; LEUKEMIA REMISSION; LYMPHADENOPATHY; LYMPHOCYTE COUNT; LYMPHOCYTOSIS; MANTLE CELL LYMPHOMA; NAUSEA; OVERALL SURVIVAL; PHASE 1 CLINICAL TRIAL (TOPIC); PROGRESSION FREE SURVIVAL; REVIEW; THROMBOCYTE AGGREGATION; UPPER RESPIRATORY TRACT INFECTION; WALDENSTROEM MACROGLOBULINEMIA;

ANTINEOPLASTIC AGENTS; CLINICAL TRIALS AS TOPIC; HUMANS; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; PROTEIN KINASE INHIBITORS; PROTEIN-TYROSINE KINASES;

EID: 84896732823     PISSN: 15588211     EISSN: 1558822X     Source Type: Journal    
DOI: 10.1007/s11899-013-0188-8     Document Type: Review

References (60)

1. Satterthwaite AB, Witte ON. The role of Bruton's tyrosine kinase in B-cell development and function: a genetic perspective. Immunol Rev. 2000;175:120-7. (Pubitemid 30427162)
2. Spaargaren M, Beuling EA, Rurup ML, Meijer HP, Klok MD, Middendorp S, et al. The B cell antigen receptor controls integrin activity through Btk and PLCgamma2. J Exp Med. 2003;198(10):1539-50. (Pubitemid 37467168)
3. Ortolano S, Hwang IY, Han SB, Kehrl JH. Roles for phosphoinositide 3-kinases, Bruton's tyrosine kinase, and Jun kinases in B lymphocyte chemotaxis and homing. Eur J Immunol. 2006;36(5):1285-95.
4. de Gorter DJ, Beuling EA, Kersseboom R, Middendorp S, van Gils JM, Hendriks RW, et al. Bruton's tyrosine kinase and phospholipase Cgamma2 mediate chemokine-controlled B cell migration and homing. Immunity. 2007;26(1):93-104. (Pubitemid 46109347)
5. Jefferies CA, Doyle S, Brunner C, Dunne A, Brint E, Wietek C, et al. Bruton's tyrosine kinase is a Toll/interleukin-1 receptor domain-binding protein that participates in nuclear factor kappaB activation by Toll-like receptor 4. J Biol Chem. 2003;278(28):26258-64. (Pubitemid 36835395)
6. Lee KG, Xu S, Kang ZH, Huo J, Huang M, Liu D, et al. Bruton's tyrosine kinase phosphorylates Toll-like receptor 3 to initiate antiviral response. Proc Natl Acad Sci U S A. 2012;109(15):5791-6.
7. Matsuda T, Takahashi-Tezuka M, Fukada T, Okuyama Y, Fujitani Y, Tsukada S, et al. Association and activation of Btk and Tec tyrosine kinases by gp130, a signal transducer of the interleukin-6 family of cytokines. Blood. 1995;85(3):627-33.
8. Takahashi-Tezuka M, Hibi M, Fujitani Y, Fukada T, Yamaguchi T, Hirano T. Tec tyrosine kinase links the cytokine receptors to PI-3 kinase probably through JAK. Oncogene. 1997;14(19):2273-82. (Pubitemid 27260719)
9. Liu X, Zhan Z, Li D, Xu L, Ma F, Zhang P, et al. Intracellular MHC class II molecules promote TLR-triggered innate immune responses by maintaining activation of the kinase Btk. Nat Immunol. 2011;12(5):416-24.
10. Quek LS, Bolen J, Watson SP. A role for Bruton's tyrosine kinase (Btk) in platelet activation by collagen. Curr Biol. 1998;8(20):1137-40. (Pubitemid 28501379)
11. Honda F, Kano H, Kanegane H, Nonoyama S, Kim ES, Lee SK, et al. The kinase Btk negatively regulates the production of reactive oxygen species and stimulation-induced apoptosis in human neutrophils. Nat Immunol. 2012;13(4):369-78.
12. Genevier HC, Hinshelwood S, Gaspar HB, Rigley KP, Brown D, Saeland S, et al. Expression of Bruton's tyrosine kinase protein within the B cell lineage. Eur J Immunol. 1994;24(12):3100-5.
13. Rawlings DJ, Saffran DC, Tsukada S, Largaespada DA, Grimaldi JC, Cohen L, et al. Mutation of unique region of Bruton's tyrosine kinase in immunodeficient XID mice. Science. 1993;261(5119):358-61. (Pubitemid 23281007)
14. Vetrie D, Vorechovsky I, Sideras P, Holland J, Davies A, Flinter F, et al. The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases. Nature. 1993;361(6409):226-33. (Pubitemid 23034471)
15. Tsukada S, Saffran DC, Rawlings DJ, Parolini O, Allen RC, Klisak I, et al. Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia. Cell. 1993;72(2):279-90. (Pubitemid 23044942)
16. Conley ME, Dobbs AK, Farmer DM, Kilic S, Paris K, Grigoriadou S, et al. Primary B cell immunodeficiencies: comparisons and contrasts. Annu Rev Immunol. 2009;27:199-227.
17. Herman SE, Gordon AL, Hertlein E, Ramanunni A, Zhang X, Jaglowski S, et al. Bruton's tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Blood. 2011 Mar 21.
18. • Ponader S, Chen SS, Buggy JJ, Balakrishnan K, Gandhi V, Wierda WG, et al. The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo. Blood. 2012;119(5):1182-9. CLL in vitro and in vivo models explain the clinical activity of ibrutinib in CLL, based on ibrutinib effects on CLL-cell migration and proliferation.
19. 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.
20. •• Honigberg LA, Smith AM, Sirisawad M, Verner E, Loury D, Chang B, et al. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious inmodels of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci U S A. 2010;107(29):13075-80. In-depth characterization of ibrutinib in preclinical models.
21. Chang BY, Huang MM, Francesco M, Chen J, Sokolove J, Magadala P, et al. The Bruton tyrosine kinase inhibitor PCI-32765 ameliorates autoimmune arthritis by inhibition of multiple effector cells. Arthritis Res Ther. 2011;13(4):R115.
22. Di Paolo JA, Huang T, Balazs M, Barbosa J, Barck KH, Bravo BJ, et al. Specific Btk inhibition suppresses B cell- and myeloid cell-mediated arthritis. Nat Chem Biol. 2011;7(1):41-50.
23. Bernal A, Pastore RD, Asgary Z, Keller SA, Cesarman E, Liou HC, et al. Survival of leukemic B cells promoted by engagement of the antigen receptor. Blood. 2001;98(10):3050-7.
24. Longo PG, Laurenti L, Gobessi S, Sica S, Leone G, Efremov DG. The Akt/Mcl-1 pathway plays a prominent role in mediating antiapoptotic signals downstream of the B-cell receptor in chronic lymphocytic leukemia B cells. Blood. 2008;111(2):846-55.
25. Gauld SB, Dal Porto JM, Cambier JC. B cell antigen receptor signaling: roles in cell development and disease. Science. 2002;296(5573):1641-2. (Pubitemid 34579149)
26. Kuppers R. Mechanisms of B-cell lymphoma pathogenesis. Nat Rev. 2005;5(4):251-62. (Pubitemid 40488631)
27. Burger JA. Nurture versus nature: the microenvironment in chronic lymphocytic leukemia. Hematol Am Soc Hematol Educ Program. 2011;2011:96-103.
28. Stevenson FK, Krysov S, Davies AJ, Steele AJ, Packham G. B-cell receptor signaling in chronic lymphocytic leukemia. Blood. 2011;118(16):4313-20.
29. Woyach JA, Johnson AJ, Byrd JC. The B-cell receptor signaling pathway as a therapeutic target in CLL. Blood. 2012;120(6):1175-84.
30. Davis RE, Ngo VN, Lenz G, Tolar P, Young RM, Romesser PB, et al. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature. 2010;463(7277):88-92.
31. Chen SS, Batliwalla F, Holodick NE, Yan XJ, Yancopoulos S, Croce CM, et al. Autoantigen can promote progression to a more aggressive TCL1 leukemia by selecting variants with enhanced Bcell receptor signaling. Proc Natl Acad Sci U S A. 2013;110(16):E1500-7.
32. Duhren-von Minden M, Ubelhart R, Schneider D, Wossning T, Bach MP, Buchner M, et al. Chronic lymphocytic leukaemia is driven by antigen-independent cell-autonomous signalling. Nature. 2012;489(7415):309-12.
33. Lenz G, Davis RE, Ngo VN, Lam L, George TC, Wright GW, et al. Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science. 2008;319(5870):1676-9. (Pubitemid 351432507)
34. Hoogeboom R, van Kessel KP, Hochstenbach F, Wormhoudt TA, Reinten RJ, Wagner K, et al. A mutated B cell chronic lymphocytic leukemia subset that recognizes and responds to fungi. J Exp Med. 2013;210(1):59-70.
35. Binder M, Lechenne B, Ummanni R, Scharf C, Balabanov S, Trusch M, et al. Stereotypical chronic lymphocytic leukemia B-cell receptors recognize survival promoting antigens on stromal cells. PLoS One. 2010;5(12):e15992.
36. Chu CC, Catera R, Hatzi K, Yan XJ, Zhang L, Wang XB, et al. Chronic lymphocytic leukemia antibodies with a common stereotypic rearrangement recognize nonmuscle myosin heavy chain IIA. Blood. 2008;112(13):5122-9.
37. Hoogeboom R, Wormhoudt TA, Schipperus MR, Langerak AW, Dunn-Walters DK, Guikema JE, et al. A novel chronic lymphocytic leukemia subset expressingmutated IGHV3-7-encoded rheumatoid factor B-cell receptors that are functionally proficient. Leukemia. 2012 Aug 20.
38. de Rooij MF, Kuil A, Geest CR, Eldering E, Chang BY, Buggy JJ, et al. The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. Blood. 2012;119(11):2590-4.
39. Schwamb J, Feldhaus V, Baumann M, Patz M, Brodesser S, Brinker R, et al. B-cell receptor triggers drug sensitivity of primary CLL cells by controlling glucosylation of ceramides. Blood. 2012;120(19):3978-85.
40. Yang Y, Shaffer 3rd AL, Emre NC, Ceribelli M, Zhang M, Wright G, et al. Exploiting synthetic lethality for the therapy of ABC diffuse large B cell lymphoma. Cancer Cell. 2012;21(6):723-37.
41. Tai YT, Chang BY, Kong SY, Fulciniti M, Yang G, Calle Y, et al. Bruton tyrosine kinase inhibition is a novel therapeutic strategy targeting tumor in the bone marrow microenvironment in multiple myeloma. Blood. 2012;120(9):1877-87.
42. Chang BY, Francesco M, De Rooij MF, Magadala P, Steggerda SM, Huang MM, et al. Egress of CD19(+)CD5(+) cells into peripheral blood following treatment with the Bruton tyrosine kinase inhibitor ibrutinib in mantle cell lymphoma patients. Blood. 2013;122(14):2412-24.
43. Burger JA, Montserrat E. Coming full circle: 70 years of chronic lymphocytic leukemia cell redistribution, from glucocorticoids to inhibitors of B-cell receptor signaling. Blood. 2013;121(9):1501-9.
44. Singh J, Petter RC, Kluge AF. Targeted covalent drugs of the kinase family. Curr Opin Chem Biol. 2010;14(4):475-80.
45. Pan Z, Scheerens H, Li SJ, Schultz BE, Sprengeler PA, Burrill LC, et al. Discovery of selective irreversible inhibitors for Bruton's tyrosine kinase. ChemMedChem. 2007;2(1):58-61.
46. Burger JA, Buggy JJ. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765). Leuk Lymphoma. 2013;54(11):2385-91.
47. Dubovsky JA, Beckwith KA, Natarajan G, Woyach JA, Jaglowski S, Zhong Y, et al. Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes. Blood. 2013;122(15):2539-49.
48. •• Wang ML, Rule S, Martin P, Goy A, Auer R, Kahl BS, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013;369(6):507-16. First paper to describe the activity of ibrutinib in MCL and a basis for the FDA approval of ibrutinib for relapsed MCL in November 2013.
49. •• Byrd JC, Furman RR, Coutre SE, Flinn IW, Burger JA, Blum KA, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369(1):32-42. First paper to describe the single-agent experience of ibrutinib in CLL.
50. Cheson BD, Byrd JC, Rai KR, Kay NE, O'Brien SM, Flinn IW, et al. Novel targeted agents and the need to refine clinical end points in chronic lymphocytic leukemia. J Clin Oncol. 2012;30(23):2820-2.
51. Friedberg JW, Sharman J, Sweetenham J, Johnston PB, Vose JM, Lacasce A, et al. Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Blood. 2010;115(13):2578-85.
52. Hoellenriegel J, Meadows SA, Sivina M, Wierda WG, Kantarjian H, Keating MJ, et al. The phosphoinositide 3′-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia. Blood. 2011;118(13):3603-12.
53. Farooqui M, Lozier JN, Valdez J, Saba N, Wells A, Soto S, et al. Ibrutinib (PCI 32765) Rapidly Improves Platelet Counts in Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL) Patients and Has Minimal Effects On Platelet Aggregation Blood. 2012;120(21):abstract 1789.
54. Liu J, Fitzgerald ME, Berndt MC, Jackson CW, Gartner TK. Bruton tyrosine kinase is essential for botrocetin/VWF-induced signaling and GPIb-dependent thrombus formation in vivo. Blood. 2006;108(8):2596-603.
55. Jackson SP, Cranmer S, Mangin P, Yuan Y. Are Erk, Btk, and PECAM-1 major players in GPIb signaling? The challenge of unraveling signaling events downstream of platelet GPIb. Blood. 2007;109(2):846-7. discussion 47-8.
56. Chang BY, Furman RR, Zapatka M, Barrientos JC, Li D, Steggerda S, et al. Use of tumor genomic profiling to reveal mechanisms of resistance to the BTK inhibitor ibrutinib in chronic lymphocytic leukemia (CLL). J Clin Oncol. 2013;31:suppl; abstr 7014.
57. Mahajan S, Ghosh S, Sudbeck EA, Zheng Y, Downs S, Hupke M, et al. Rational design and synthesis of a novel anti-leukemic agent targeting Bruton's tyrosine kinase (BTK), LFM-A13 [alpha-cyano-beta-hydroxy-beta-methyl-N-(2, 5-dibromophenyl)propenamide]. J Biol Chem. 1999;274(14):9587-99.
58. Uckun FM, Tibbles H, Venkatachalam T, DuMez D, Erbeck D. Preclinical toxicity and pharmacokinetics of the Bruton's tyrosine kinase-targeting anti-leukemic drug candidate, alpha-cyano-beta-hydroxy-beta-methyl-N- (2,5-dibromophenyl) propenamide (LFM-A13). Arzneimittelforschung. 2007;57(1):31-46. (Pubitemid 46212986)
59. Evans EK, Tester R, Aslanian S, Karp R, Sheets M, Labenski MT, et al. Inhibition of Btk with CC-292 Provides Early Pharmacodynamic Assessment of Activity in Mice and Humans. J Pharmacol Exp Ther. 2013 May 24.
60. Burger JA, Keating MJ, Wierda WG, Hoellenriegel J, Ferrajoli A, Faderl S, et al. The Btk Inhibitor Ibrutinib (PCI-32765) in Combination with Rituximab Is Well Tolerated and Displays Profound Activity in High-Risk Chronic Lymphocytic Leukemia (CLL) Patients Blood. 2012;120(21):Abstract 187.