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Review

Cardiac side effects of bruton tyrosine kinase (BTK) inhibitors

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Pages 1554-1564 | Received 18 Jul 2017, Accepted 30 Aug 2017, Published online: 13 Sep 2017

References

  • Herman SEM, Gordon AL, Hertlein E, et al. Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Blood. 2011;117:6287–6296.
  • Honigberg LA, Smith AM, Sirisawad M, et al. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci USA. 2010;107:13075–13080.
  • Cheng S, Ma J, Guo A, et al. BTK inhibition targets in vivo CLL proliferation through its effects on B-cell receptor signaling activity. Leukaemia. 2014;28:649–657.
  • Byrd JC, Furman RR, Coutre SE, et al. Three-year follow-up of treatment-naive and previously treated patients with CLL and SLL receiving single-agent ibrutinib. Blood. 2015;125:2497–2506.
  • Burger JA, Tedeschi A, Barr PM, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015;373:2425–2437.
  • Wang ML, Blum KA, Martin P, et al. Long-term follow-up of MCL patients treated with single-agent ibrutinib: updated safety and efficacy results. Blood. 2015;126:739–745.
  • Treon SP, Tripsas CK, Meid K, et al. Ibrutinib in previously treated Waldenström’s macroglobulinemia. N Engl J Med. 2015;372:1430–1440.
  • Gertz MA. Waldenström macroglobulinemia: 2017 update on diagnosis, risk stratification, and management. Am J Hematol. 2017;92:209–217.
  • Ponader S, Chen SS, Buggy JJ, 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;119:1182–1189.
  • de Rooij MFM, Kuil A, Geest CR, 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;119:2590–2594.
  • Herman SEM, Mustafa RZ, Gyamfi JA, et al. Ibrutinib inhibits BCR and NF- B signaling and reduces tumor proliferation in tissue-resident cells of patients with CLL. Blood. 2014;123:3286–3295.
  • Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2007. CA Cancer J Clin. 2007;57:43–66.
  • Rozman C, Montserrat E. Chronic lymphocytic leukaemia. N Engl J Med. 1995;333:1515.
  • Woyach JA, Johnson AJ, Byrd JC. The B-cell receptor signaling pathway as a therapeutic target in CLL. Blood. 2012;120:1175–1184.
  • Minden MD-V, Übelhart R, Schneider D, et al. Chronic lymphocytic leukaemia is driven by antigen-independent cell-autonomous signalling. Nature. 2012;489:309–312.
  • Mohamed AJ, Yu L, Bäckesjö C-M, et al. Bruton’s tyrosine kinase (Btk): function, regulation, and transformation with special emphasis on the PH domain. Immunol Rev. 2009;228:58–73.
  • Takata M, Kurosaki T. A role for Bruton's tyrosine kinase in B cell antigen receptor-mediated activation of phospholipase C-gamma 2. J Exp Med. 1996;184:31–40.
  • Burger JA, Chiorazzi N. B cell receptor signaling in chronic lymphocytic leukemia. Trends Immunol. 2013;34:592–601.
  • Okkenhaug K, Vanhaesebroeck B. PI3K in lymphocyte development, differentiation and activation. Nat Rev Immunol. 2003;3:317–330.
  • Hoellenriegel J, Meadows SA, Sivina M, et al. The phosphoinositide 3′-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia. Blood. 2011;118:3603–3612.
  • Hacken ten E, Burger JA. Microenvironment interactions and B-cell receptor signaling in chronic lymphocytic leukemia: implications for disease pathogenesis and treatment. BBA - Mol Cell Res. 2016;1863:401–413.
  • Byrd JC, Furman RR, Coutre SE, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369:32–42.
  • Chanan-Khan A, Cramer P, Demirkan F, et al. Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study. Lancet Oncol. 2016;17:200–211.
  • O'Brien S, Jones JA, Coutre SE, et al. Ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia with 17p deletion (RESONATE-17): a phase 2, open-label, multicentre study. Lancet Oncol. 2016;17(10):1409–1418.
  • Barr P. Updated efficacy and safety from the phase 3 resonate-2 study: ibrutinib as first-line treatment option in patients 65 years and older with chronic lymphocytic leukemia/small lymphocytic leukemia. Blood. 2016;128:234.
  • Farooqui MZH, Valdez J, Martyr S, et al. Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations: a phase 2, single-arm trial. Lancet Oncol. 2015;16:169–176.
  • Byrd JC, Brown JR, O'Brien S, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014;371:213–223.
  • Jaglowski SM, Jones JA, Nagar V, et al. Safety and activity of BTK inhibitor ibrutinib combined with ofatumumab in chronic lymphocytic leukemia: a phase 1b/2 study. Blood. 2015;126:842–850.
  • Burger JA, Keating MJ, Wierda WG, et al. Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study. Lancet Oncol. 2014;15:1090–1099.
  • Rossi D, Terzi-di-Bergamo L, De Paoli L, et al. Molecular prediction of durable remission after first-line fludarabine-cyclophosphamide-rituximab in chronic lymphocytic leukemia. Blood. 2015;126:1921–1924.
  • Zenz T, Eichhorst B, Busch R, et al. TP53 mutation and survival in chronic lymphocytic leukemia. J Clin Oncol. 2010;28:4473–4479.
  • Fischer K, Bahlo J, Fink AM, et al. Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial. Blood. 2016;127:208–215.
  • Thompson PA, Wierda WG. Eliminating minimal residual disease as a therapeutic end point: working toward cure for patients with CLL. Blood. 2016;127:279–286.
  • Imbruvica prescribing information. 2017. https://www.imbruvica.comdocslibrariesproviderdefault-document-libraryprescribinginformation.pdf.
  • Wang ML, Rule S, Martin P, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013;369:507–516.
  • Dreyling M, Jurczak W, Jerkeman 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;387:770–778.
  • Owen RG, Kyle RA, Stone MJ, et al. Response assessment in Waldenström macroglobulinaemia: update from the VIth International Workshop. Br J Haematol. 2012;160:171–176.
  • Treon SP, Xu L, Yang G, et al. MYD88 L265P somatic mutation in Waldenström's macroglobulinemia. N Engl J Med. 2012;367:826–833.
  • Xu L, Hunter ZR, Yang G, et al. MYD88 L265P in Waldenström macroglobulinemia, immunoglobulin M monoclonal gammopathy, and other B-cell lymphoproliferative disorders using conventional and quantitative allele-specific polymerase chain reaction. Blood. 2013;121:2051–2058.
  • Dimopoulos MA, Trotman J, Tedeschi A, et al. Ibrutinib for patients with rituximab-refractory Waldenström's macroglobulinaemia (iNNOVATE): an open-label substudy of an international, multicentre, phase 3 trial. Lancet Oncol. 2017;18:241–250.
  • Stewart DM, Tian L, Nelson DL. The clinical spectrum of bruton’s agammaglobulinemia. Curr Allergy Asthma Rep. 2001;1:558–565.
  • Leong DP, Caron F, Hillis C, et al. The risk of atrial fibrillation with ibrutinib use: a systematic review and meta-analysis. Blood. 2016;128:138–140.
  • Shanafelt TD, Parikh SA, Noseworthy PA, et al. Atrial fibrillation in patients with chronic lymphocytic leukemia (CLL). Leuk Lymphoma. 2017;58:1630–1639.
  • Farooqui M, Wiestner A, Valdez J. Atrial Fibrillation in CLL/SLL Patients on Ibrutinib. 2015.
  • Coutre SE, Furman RR, Flinn IW, et al. Extended treatment with single-agent ibrutinib at the 420 mg dose leads to durable responses in chronic lymphocytic leukemia/small lymphocytic lymphoma. Clin Cancer Res. 2017;23:1149–1155.
  • Jain P, Keating MJ, Wierda WG, et al. Long-term follow-up of treatment with ibrutinib and rituximab in patients with high-risk chronic lymphocytic leukemia. Clin Cancer Res. 2016;23:2154–2158.
  • Mato AR, Nabhan C, Barr PM, et al. Outcomes of CLL patients treated with sequential kinase inhibitor therapy: a real world experience. Blood. 2016;128:2199–2205.
  • Jain P, Thompson PA, Keating M, et al. Long-term outcomes for patients with chronic lymphocytic leukemia who discontinue ibrutinib. Cancer. 2017;123:2268–2273.
  • Maddocks K, Jones JA. Bruton tyrosine kinase inhibition in chronic lymphocytic leukemia. Semin Oncol. 2016;43:251–259.
  • Jain P, Keating M, Wierda W, et al. Outcomes of patients with chronic lymphocytic leukemia after discontinuing ibrutinib. Blood. 2015;125:2062–2067.
  • Thompson PA, Cymbalista F, Keating M, Tam CS. The impact of atrial fibrillation on subsequent survival of patients receiving ibrutinib as treatment of chronic lymphocytic leukemia (CLL): An International Study. 2016.
  • Thompson PA, Lévy V, Tam CS, et al. Atrial fibrillation in CLL patients treated with ibrutinib. An international retrospective study. Br J Haematol. 2016;175:462–466.
  • Fauchier L, Villejoubert O, Clementy N, et al. Causes of death and influencing factors in patients with atrial fibrillation. Am J Med. 2016;129:1278–1287.
  • Mato A, Carver J. Left Atrial Abnormality as a Predictor of ibrutinib-associated atrial fibrillation in patients with chronic lymphocytic leukemia. XVII International Workshop on Chronic Lymphocytic Leukaemia. 2017.
  • Lampson BL, Yu L, Glynn RJ, et al. Ventricular arrhythmias and sudden death in patients taking ibrutinib. Blood. 2017;129:2581–2584.
  • Tomcsányi J, Nényei Z, Mátrai Z, et al. Ibrutinib, an approved tyrosine kinase inhibitor as a potential cause of recurrent polymorphic ventricular tachycardia. JACC: Clin Electrophysiol. 2016;2:847–849.
  • McMullen JR, Boey EJH, Ooi JYY, et al. Ibrutinib increases the risk of atrial fibrillation, potentially through inhibition of cardiac PI3K-Akt signaling. Blood. 2014;124:3829–3830.
  • Qiu Y, Kung HJ. Signaling network of the Btk family kinases. Oncogene. 2000;19:5651–5661.
  • Pretorius L, Du XJ, Woodcock EA, et al. Reduced phosphoinositide 3-kinase (p110α) activation increases the susceptibility to atrial fibrillation. Am J Pathol. 2010;175:998–1009.
  • Yang T, Moleslehi J, Roden DM. Proarrhythmic effects of ibrutinib, a clinically approved inhibitor of Bruton’S tyrosine kinase (BTK) used in cancer therapy. Circulation. 2015;132(Supp 3):A14587.
  • Nair KS, Cheson B. The role of idelalisib in the treatment of relapsed and refractory chronic lymphocytic leukemia. Ther Adv Hematol. 2016;7:69–84.
  • Chung C, Lee R. Ibrutinib, obinutuzumab, idelalisib, and beyond: review of novel and evolving therapies for chronic lymphocytic leukemia. Pharmacotherapy. 2014;34:1298–1316.
  • January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014;64(21):e1–76.
  • Atkinson BT. Tec regulates platelet activation by GPVI in the absence of Btk. Blood. 2003;102:3592–3599.
  • Levade M, David E, Garcia C, et al. Ibrutinib treatment affects collagen and von Willebrand factor-dependent platelet functions. Blood. 2014;124:3991–3995.
  • Kamel S, Horton L, Ysebaert L, et al. Ibrutinib inhibits collagen-mediated but not ADP-mediated platelet aggregation. Leukaemia. 2015;29:783–787.
  • Jones JA, Hillmen P, Coutre S, et al. Use of anticoagulants and antiplatelet in patients with chronic lymphocytic leukaemia treated with single-agent ibrutinib. Br J Haematol. 2017;102:3516–3592.
  • Lipsky AH, Farooqui MZH, Tian X, et al. Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib. Haematologica. 2015;100:1571–1578.
  • Shatzel JJ, Olson SR, Tao DL, et al. Ibrutinib-associated bleeding: pathogenesis, management and risk reduction strategies. J Thromb Haemost. 2017;32(Suppl. 1):1830.
  • FDA. 2015. [Internet]. http://www.accessdata.fda.govdrugsatfdadocslabel-slbl.pdf. 2015;1–26.
  • European Medicines Agency. http://www.ema.europa.eudocsenGBdocumentlibraryEPAR-ProductInformationhumanWC.pdf. 2017;1–37.
  • Chai-Adisaksopha C, Crowther M, Isayama T, et al. The impact of bleeding complications in patients receiving target-specific oral anticoagulants: a systematic review and meta-analysis. Blood. 2014;124:2450–2458.
  • Scheers E, Leclercq L, de Jong J, et al. Absorption, metabolism, and excretion of oral 14C radiolabeled ibrutinib: an open-label, phase I, single-dose study in healthy men. Drug Metab. Dispos. 2015;43:289–297.
  • de Jong J, Skee D, Murphy J, et al. Effect of CYP3A perpetrators on ibrutinib exposure in healthy participants. Pharmacol Res Perspect. 2015;3:e00156.
  • Poli D, Antonucci E, Pengo V, et al. Comparison of HAS-BLED and HAS-BED versus CHADS2 and CHA2DS2VASC stroke and bleeding scores in patients with atrial fibrillation. Am J Cardiol. 2017;119:1012–1016.
  • Lip GYH, Lane DA. Bleeding risk assessment in atrial fibrillation: observations on the use and misuse of bleeding risk scores. J Thromb Haemost. 2016;14:1711–1714.
  • Lip GYH. Recommendations for thromboprophylaxis in the 2012 focused update of the ESC guidelines on atrial fibrillation: a commentary. J Thromb Haemost. 2013;11:615–626.
  • Chai KL, Rowan G, Seymour JF, et al. Practical recommendations for the choice of anticoagulants in the management of patients with atrial fibrillation on ibrutinib. Leuk. Lymphoma. 2017;128:1–4.
  • Finnes HD, Chaffee KG, Call TG, et al. Pharmacovigilance during ibrutinib therapy for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) in routine clinical practice. Leuk. Lymphoma. 2017;58:1376–1383.
  • Roy D, Talajic M, Nattel S, et al. Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med. 2008;358:2667–2677.
  • Chinitz JS, Halperin JL, Reddy VY, et al. Rate or rhythm control for atrial fibrillation: update and controversies. Am J Med. 2012;125:1049–1056.
  • Barr PM, Brown JR, Hillmen P, et al. Impact of ibrutinib dose adherence on therapeutic efficacy in patients with previously treated CLL/SLL. Blood. 2017;129:2612–2615.
  • Harrington B, Johnson AJ, Gulrajani M, et al. ACP-196 is a second generation inhibitor of bruton tyrosine kinase (BTK) with enhanced target specificity. Blood. 2015;126:2908.
  • Wu J, Zhang M, Liu D. Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor. J Hematol Oncol. 2016;9:21.
  • Byrd JC, Harrington B, O'Brien S, et al. Acalabrutinib (ACP-196) in relapsed chronic lymphocytic leukemia. N Engl J Med. 2016;374:323–332.
  • Tam CS, Grigg AP, Opat S. The BTK inhibitor, Bgb-3111, is safe, tolerable, and highly active in patients with relapsed/refractory B-cell malignancies: initial report of a phase 1 first-in-human trial. Blood. 2015;126:832.
  • Tam CS, Seymour J, Grigg AP. High major response rate, including very good partial responses (VGPR), in patients (pts) with Waldenstrom macroglobulinemia (WM) treated with the highly specific BTK inhibitor Bgb-3111: expansion phase results from an ongoing phase I study. Blood. 2016;128:1216.
  • Walter HS, Rule SA, Dyer MJS, et al. A phase 1 clinical trial of the selective BTK inhibitor ONO/GS-4059 in relapsed and refractory mature B-cell malignancies. Blood. 2016;127:411–419.
  • Walter HS, Jayne S, Rule SA, et al. Long-term follow-up of patients with CLL treated with the selective Bruton's tyrosine kinase inhibitor ONO/GS-4059. Blood. 2017;129:2808–2810.
  • Elevate CLL R/R: Study of Acalabrutinib (ACP-196) Versus Ibrutinib in Previously Treated Subjects With High Risk Chronic Lymphocytic Leukemia. http:sclinicaltrials.govctshowNCT. 2017.

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