Evidence-based ibrutinib-related adverse reactions and pharmaceutical care

doi:10.19803/j.1672-8629.2022.07.26

Abstract

Abstract: Ibrutinib, a small molecule BTK inhibitor, is the first targeted drug mainly used for B cell malignant tumors. With the increase of related research at home and abroad, more and more adverse reactions induced by ibrutinib have been discovered, such as bleeding, atrial fibrillation, hypertension, infection, diarrhea, arthralgia/myalgia, skin toxicity, and hematological toxicity. Ibrutinib has been associated with an increased risk of grade 1 ~ 2 toxicities. Serious adverse events are rare. Based on literature, this article summarizes the types, incidence, prevention, management, and pharmaceutical care of common as well as rare but important toxicities of ibrutinib. It is expected to provide evidence-based recommendations and minimize side effects.

Key words: ibrutinib, adverse drug reaction, pharmaceutical care, evidence-based

CLC Number:

LI Yanming, ZHAO Zhigang. Evidence-based ibrutinib-related adverse reactions and pharmaceutical care[J]. Chinese Journal of Pharmacovigilance, 2022, 19(7): 807-811.

References

[1] SIVINA M, KREITMAN RJ, ARONS E, et al.The bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) blocks hairy cell leukaemia survival, proliferation and B cell receptor signalling: a new therapeutic approach[J]. Br J Haematol, 2014, 166(2): 177-188.
[2] WANG J, LIU X, HONG Y, et al.Ibrutinib, a Bruton's tyrosine kinase inhibitor, exhibits antitumoral activity and induces autophagy in glioblastoma[J]. J Exp Clin Canc Res, 2017, 36(1): 96.
[3] SOUSSAIN C, CHOQUET S, BLONSKI M, 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) andthe French oculo-cerebral lymphoma (LOC) network[J]. Eur J Cancer, 2019, (8)117: 121-130.
[4] RICHARDSON PG, BENSINGER WI, HUFF CA, et al.Ibrutinib alone or with dexamethasone for relapsed or relapsed and refractory multiple myeloma: phase 2 trial results[J]. Br J Haematol, 2018, 180(6): 821-830.
[5] AL-TOUBAH T, SCHELL MJ, CIVES M, et al.A phase ii study of ibrutinib in advanced neuroendocrine neoplasms[J]. Neuroend-ocrinology, 2020, 110(5): 377-383.
[6] HOU K, YU Z, JIA Y, et al.Efficacy and safety of ibrutinib in diffuse large B-cell lymphoma: a single-arm meta-analysis[J]. Crit Rev Oncol Hematol, 2020, 152(8): 103010.
[7] STEPHENS DM, BYRD JC.How I manage ibrutinib intolerance and complications in patients with chronic lymphocytic leukemia[J]. Blood, 2019, 133(12): 1298-1307.
[8] ALLOUCHERY M, TOMOWIAK C, GUIDEZ S, et al.Patterns of use and safety of ibrutinib in real-life practice[J]. Br J Clin Pharmacol, 2021, 87(3): 895-904.
[9] BYRD JC, FURMAN RR, COUTRE SE, et al.Three-year follow-up of treatment-naïve and previously treated patients with CLL and SLL receiving single-agent ibrutinib[J]. Blood, 2015, 125(16): 2497-2506.
[10] National Institutes of Health, National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) Version 5[R/OL].(2017-11-27)[2020-06-30]. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm.
[11] BROWN JR, MOSLEHI J, EWER MS, et al.Incidence of and risk factors for major haemorrhage in patients treated with ibrutinib: an integrated analysis[J]. Br J Haematol, 2019, 184(4): 558-569.
[12] MOCK J, KUNK PR, PALKIMAS S, et al.Risk of major bleeding with ibrutinib[J]. Clin Lymphoma Myeloma Leuk, 2018, 18(11):755-761.
[13] CALDEIRA D, ALVES D, COSTA J, et al.Ibrutinib increases the risk of hypertension and atrial fibrillation: systematic review and meta-analysis[J]. PLoS One, 2019, 14(2): e0211228.
[14] BROWN JR, MOSLEHI J, O'BRIEN S, et al. Characterization of atrial fibrillation adverse events reported in ibrutinib randomized controlled registration trials[J]. Haematologica,2017, 102(10): 1796-1805.
[15] BYRD JC, FURMAN RR, COUTRE SE, et al.Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia[J]. N Engl J Med, 2013, 369(1): 32-42.
[16] BARR PM, ROBAK T, OWEN C, et al.Sustained efficacy and detailed clinical follow-up of first-line ibrutinib treatment in older patients with chronic lymphocytic leukemia: extended phase 3 results from RESONATE-2[J]. Haematologica, 2018, 103(9): 1502-1510.
[17] DICKERSON T, WICZER T, WALLER A, et al.Hypertension and incident cardiovascular events following ibrutinib initiation[J]. Blood, 2019, 134(22): 1919-1928.
[18] TILLMAN BF, PAUFF JM, SATYANARAYANA G, et al.Systematic review of infectious events with the Bruton tyrosine kinase inhibitor ibrutinib in the treatment of hematologic malignancies[J]. Eur J Haematol, 2018, 100(4): 325-334.
[19] VARUGHESE T, TAUR Y, COHEN N, et al.Serious infections in patients receiving ibrutinib for treatment of lymphoid cancer[J].Clin Infect Dis, 2018, 67(5): 687-692.
[20] ROGERS KA, LUAY M, ZHAO Q, et al.Incidence and type of opportunistic infections during ibrutinib treatment at a single academic center[J]. Blood, 2017, 130(S1): 830.
[21] LIU MY, CAI J, YAO Y, et al.Literature analysis of invasive fungal infections induced by ibrutinib[J]. Chinese Journal of Pharmacoepidemiology(药物流行病学杂志), 2020, 29(9): 647-651.
[22] BALL S, DAS A, VUTTHIKRAIVIT W, et al.Risk of infection associated with ibrutinib in patients with b-cell malignancies: a systematic review and meta-analysis of randomized controlled trials[J]. Clin Lymphoma Myeloma Leuk, 2020, 20(2): 87-97.
[23] ZHOU Y, LU H, YANG M, et al.Adverse drug events associated with ibrutinib for the treatment of elderly patients with chronic lymphocytic leukemia: a systematic review and meta-analysis of randomized trials[J]. Medicine, 2019, 98(33): e16915.
[24] BROWN JR, HILLMEN P, O' BRIEN S, et al. Extended follow-up and impact of high-risk prognostic factors from the phase 3 RESONATE study in patients with previously treated CLL/SLL[J]. Leukemia, 2018, 32(1): 83-91.
[25] PAYDAS S.Management of adverse effects/toxicity of ibrutinib[J].Crit Rev Oncol Hematol, 2019, 136: 56-63.
[26] SIBAUD V, BEYLOT-BARRY M, PROTIN C, et al.Dermatological toxicities of bruton's tyrosine kinase inhibitors[J]. American Journal of Clinical Dermatology, 2020 21(6): 799-812.
[27] IBERRI DJ, KWONG BY, STEVENS LA, et al.Ibrutinib-associated rash: a single-centre experience of clinicopathological features and management[J]. Br J Haematol, 2018, 180(1): 164-166.
[28] STEWART J, BAYERS S, VANDERGRIFF T.Self-limiting ibrutinib-induced neutrophilic panniculitis[J]. Am J Dermato-pathol, 2018, 40(2): e28-e29.
[29] BITAR C, FAROOQUI MZ, VALDEZ J, et al.Hair and nail changes during long-term therapy with ibrutinib for chronic lymphocytic leukemia[J]. JAMA Dermatol, 2016, 152(6): 698-701.
[30] BYRD JC, BROWN JR, O'BRIEN S, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia[J]. N Engl J Med, 2014, 371(3): 213-223.
[31] BURGER JA, TEDESCHI A, BARR PM, et al.Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia[J]. N Engl J Med, 2015, 373(25): 2425-2437.
[32] RHODES JM, LORE VA 3rd, MATO AR, et al. Ibrutinib-associated arthralgias/myalgias in patients with chronic lymphocytic leukemia: incidence and impact on clinical outcomes[J]. Clin Lymphoma Myeloma Leuk, 2020, 20(7): 438-444.
[33] COUTRE SE, BYRD JC, HILLMEN P, et al.Long-term safety of single-agent ibrutinib in patients with chronic lymphocytic leukemia in 3 pivotal studies[J]. Blood Adv, 2019, 3(12): 1799-1807.
[34] PUŁA A, STAWISKI K, BRAUN M, et al. Efficacy and safety of B-cell receptor signaling pathway inhibitors in relapsed/refractory chronic lymphocytic leukemia: a systematic review and meta-analysis of randomized clinical trials[J]. Leuk Lymphoma, 2018, 59(5): 1084-1094.
[35] HERMAN SE, NIEMANN CU, FAROOQUI M, et al.Ibrutinib-induced lymphocytosis in patients with chronic lymphocytic leukemia: correlative analyses from a phase II study[J]. Leukemia, 2014, 28(11): 2188-2196.
[36] ROGERS KA, RUPPERT AS, BINGMAN A, et al.Incidence and description of autoimmune cytopenias during treatment with ibrutinib for chronic lymphocytic leukemia[J]. Leukemia, 2016, 30(2): 346-350.
[37] TAFESH ZH, COLEMAN M, FULMER C, et al.Severe hepatot-oxicity due to ibrutinib with a review of published cases[J]. Case Rep Gastroenterol, 2019, 13(2): 357-363.
[38] HERISHANU Y, KATCHMAN H, POLLIACK A.Severe hepatitis B virus reactivation related to ibrutinib monotherapy[J]. Ann Hematol, 2017, 96(4): 689-690.
[39] MOLICA S, LEVATO L, MIRABELLI R.Chronic lymphocytic leukemia, autoimmune hemolytic anemia and ibrutinib: a case report and review of the literature[J]. Leuk Lymphoma, 2016, 57(3): 735-737.
[40] ATKINSON BT, ELLMEIER W, WATSON SP.Tec regulates platelet activation by GPVI in the absence of Btk[J]. Blood, 2003, 102(10): 3592-3599.
[41] CHEN J, KINOSHITA T, GURURAJA T, et al.The effect of Bruton's tyrosine kinase (BTK) inhibitors on collagen‐induced platelet aggregation, BTK, and tyrosine kinase expressed in hepatocellular carcinoma (TEC)[J]. European Journal of Haematology, 2018, 101(5): 604-612.
[42] MCMULLEN JR, BOEY EJ, OOI JY, et al.Ibrutinib increases the risk of atrial fibrillation, potentially through inhibition of cardiac PI3K-Akt signaling[J]. Blood, 2014, 124(25): 3829-3830.
[43] JIANG L, LI L, RUAN Y, et al.Ibrutinib promotes atrial fibrillation by inducing structural remodeling and calcium dysregulation in the atrium[J]. Heart Rhythm, 2019, 16(9): 1374-1382.
[44] DUBOVSKY JA, BECKWITH KA, NATARAJAN G, et al.Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes[J]. Blood, 2013, 122(15): 2539-2549.
[45] KOHRT HE, SAGIV-BARFI I, RAFIQ S, et al.Ibrutinib (PCI-32765) antagonizes rituximab-dependent NK-cell mediated cytotoxicity[J]. Blood, 2013, 122(21): 373.
[46] ZERBIT J, CHEVRET S, BERNARD S, et al.Improved time to treatment failure and survival in ibrutinib-treated malignancies with a pharmaceutical care program: an observational cohort study[J]. Ann Hematol, 2020, 99(7): 1615-1625.
[47] 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[J]. Drug Metab Dispos. 2015, 43(2): 289-297.
[48] DE JONG J, SKEE D, MURPHY J, et al.Effect of CYP3A perpetrators on ibrutinib exposure in healthy participants[J].Pharmacology Research & Perspectives, 2015, 3(4): 00156.
[49] TREON SP, TRIPSAS CK, MEID K, et al.Ibrutinib in previously treated Waldenström's macroglobulinemia[J]. N Engl J Med, 2015, 372(15): 1430-1440.
[50] KAPELIOS CJ, BONOU MS, DIAMANTOPOULOS P, et al.Ibrutinib-related atrial fibrillation: therapeutic challenges[J].Journal of Oncology Pharmacy Practice, 2019, 25(5): 1258-1260.
[51] LASICA M, TAM CS.Management of ibrutinib toxicities: a practical guide[J]. Curr Hematol Malig Rep, 2020, 15(3): 177-186.