{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T21:34:12Z","timestamp":1768253652358,"version":"3.49.0"},"reference-count":111,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T00:00:00Z","timestamp":1681776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"BeiGene (Canada) ULC"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>The most common forms of B-cell malignancy, non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL), have seen a drastic shift in the treatment landscape over the last two decades with the introduction of targeted agents. Among them are Bruton\u2019s tyrosine kinase (BTK) inhibitors, which have demonstrated excellent efficacy in indolent B-cell NHLs and CLL. Although BTK inhibitors are generally thought to be more tolerable than chemoimmunotherapy, they are associated with a unique safety profile including varying rates of rash, diarrhea, musculoskeletal events, cardiovascular events, and bleeding. Ibrutinib was the first BTK inhibitor to gain a Health Canada indication, followed by second-generation BTK inhibitors acalabrutinib and zanubrutinib, which have better safety profiles compared to ibrutinib, likely due to their improved selectivity for BTK. As BTK inhibitors are oral agents given continuously until disease progression, long-term adverse event (AE) monitoring and management as well as polypharmacy considerations are important for maintaining patient quality of life. This paper intends to serve as a reference for Canadian nurses and pharmacists on dosing, co-administration, and AE management strategies when caring for patients with indolent B-cell NHL or CLL being treated with BTK inhibitors.<\/jats:p>","DOI":"10.3390\/curroncol30040322","type":"journal-article","created":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T05:18:13Z","timestamp":1681795093000},"page":"4222-4245","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["How We Manage Patients with Indolent B-Cell Malignancies on Bruton\u2019s Tyrosine Kinase Inhibitors: Practical Considerations for Nurses and Pharmacists"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0954-371X","authenticated-orcid":false,"given":"Shannon","family":"Nixon","sequence":"first","affiliation":[{"name":"Malignant Hematology, Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominic","family":"Duquette","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, H\u00f4pital de l\u2019Enfant-J\u00e9sus, CHU de Qu\u00e9bec-Universit\u00e9 Laval, Quebec City, QC G1J 1Z4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Doucette","sequence":"additional","affiliation":[{"name":"Impact Medicom Inc., Toronto, ON M6S 3K2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Francois","family":"Larouche","sequence":"additional","affiliation":[{"name":"Department of Medicine, CHU de Qu\u00e9bec-Universit\u00e9 Laval, Quebec City, QC G1J 1Z4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,18]]},"reference":[{"key":"ref_1","unstructured":"Statistics Canada (2022, December 20). Table: 13-10-0111-01: Number and Rates of New Cases of Primary Cancer, by Cancer Type, Age Group and Sex. Available online: https:\/\/www150.statcan.gc.ca\/t1\/tbl1\/en\/tv.action?pid=1310011101."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1038\/s41375-022-01620-2","article-title":"The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms","volume":"36","author":"Alaggio","year":"2022","journal-title":"Leukemia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1002\/ajh.24086","article-title":"Non-Hodgkin lymphoma subtype distribution, geodemographic patterns, and survival in the US: A longitudinal analysis of the National Cancer Data Base from 1998 to 2011","volume":"90","author":"Habermann","year":"2015","journal-title":"Am. J. Hematol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1002\/cncr.27773","article-title":"Survival of patients with marginal zone lymphoma","volume":"119","author":"Olszewski","year":"2013","journal-title":"Cancer"},{"key":"ref_5","unstructured":"Surveillance, Epidemiology, and End Results Program (2022, December 20). Cancer Stat Facts: NHL\u2014Follicular Lymphoma, Available online: https:\/\/seer.cancer.gov\/statfacts\/html\/follicular.html."},{"key":"ref_6","unstructured":"Surveillance, Epidemiology, and End Results Program (2022, December 20). Cancer Stat Facts: Leukemia\u2014Chronic Lymphocytic Leukemia, Available online: https:\/\/seer.cancer.gov\/statfacts\/html\/clyl.html."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/S1470-2045(14)70027-0","article-title":"Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: An open-label randomised phase 3 trial","volume":"15","author":"Ardeshna","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/s41375-020-01072-6","article-title":"Inhibitors targeting Bruton\u2019s tyrosine kinase in cancers: Drug development advances","volume":"35","author":"Wen","year":"2021","journal-title":"Leukemia"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1056\/NEJMoa1215637","article-title":"Targeting BTK with Ibrutinib in Relapsed Chronic Lymphocytic Leukemia","volume":"369","author":"Byrd","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_10","unstructured":"BeiGene Switzerland GmbH (2023, January 04). Product Monograph PrBRUKINSA\u00ae. Available online: https:\/\/www.beigene.ca\/PDF\/BRUKINSA_CA_Product_Monograph_English.pdf."},{"key":"ref_11","unstructured":"AstraZeneca Canada Inc. (2023, January 04). Product Monograph PrCALQUENCE\u00ae. Available online: https:\/\/www.astrazeneca.ca\/content\/dam\/az-ca\/downloads\/productinformation\/calquence-product-monograph-en.pdf."},{"key":"ref_12","unstructured":"Janssen Inc. (2023, January 04). Product Monograph PrIMBRUVICA\u00ae. Available online: https:\/\/www.janssen.com\/canada\/sites\/www_janssen_com_canada\/files\/prod_files\/live\/imbruvica_cpm.pdf."},{"key":"ref_13","unstructured":"European Medicines Agency (2023, January 19). Brukinsa (zanubrutinib). Available online: https:\/\/www.ema.europa.eu\/en\/documents\/overview\/brukinsa-epar-medicine-overview_en.pdf."},{"key":"ref_14","unstructured":"BeiGene, Ltd. (2023, January 19). BeiGene reports second quarter 2022 financial results. Available online: https:\/\/ir.beigene.com\/news\/beigene-reports-second-quarter-2022-financial-results\/ac313a7f-ec4a-40db-9475-9759b3804dca\/."},{"key":"ref_15","unstructured":"BeiGene USA, Inc. (2023, April 04). Highlights of Prescribing Information BRUKINSA\u00ae (zanubrutinib). Available online: https:\/\/www.brukinsa.com\/prescribing-information.pdf."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1182\/blood.2021014960","article-title":"Long-term outcomes for ibrutinib-rituximab and chemoimmunotherapy in CLL: Updated results of the E1912 trial","volume":"140","author":"Shanafelt","year":"2022","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1182\/bloodadvances.2021006434","article-title":"Up to 8-year follow-up from RESONATE-2: First-line ibrutinib treatment for patients with chronic lymphocytic leukemia","volume":"6","author":"Barr","year":"2022","journal-title":"Blood Adv."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.3324\/haematol.2021.279012","article-title":"First-line treatment of chronic lymphocytic leukemia with ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab: Final analysis of the randomized, phase III iLLUMINATE trial","volume":"107","author":"Moreno","year":"2022","journal-title":"Haematologica"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7539","DOI":"10.1200\/JCO.2022.40.16_suppl.7539","article-title":"Acalabrutinib \u00b1 obinutuzumab versus obinutuzumab + chlorambucil in treatment-na\u00efve chronic lymphocytic leukemia: Five-year follow-up of ELEVATE-TN","volume":"40","author":"Sharman","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/S1470-2045(22)00293-5","article-title":"Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): A randomised, controlled, phase 3 trial","volume":"23","author":"Tam","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1016\/S1470-2045(20)30443-5","article-title":"Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): Follow-up results from a multicentre, open-label, randomised, phase 3 trial","volume":"21","author":"Zhang","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1056\/NEJMoa1815281","article-title":"Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions","volume":"380","author":"Fischer","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_23","unstructured":"Surveillance, Epidemiology, and End Results Program (2022, December 20). Cancer Stat Facts: Non-Hodgkin Lymphoma, Available online: https:\/\/seer.cancer.gov\/statfacts\/html\/nhl.html."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1200\/JCO.2012.42.7906","article-title":"Bruton Tyrosine Kinase Inhibitor Ibrutinib (PCI-32765) Has Significant Activity in Patients With Relapsed\/Refractory B-Cell Malignancies","volume":"31","author":"Advani","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1056\/NEJMoa1509981","article-title":"Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia","volume":"374","author":"Byrd","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1182\/blood.2019001160","article-title":"Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL","volume":"134","author":"Tam","year":"2019","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1080\/17512433.2021.1978288","article-title":"Clinical pharmacology and PK\/PD translation of the second-generation Bruton\u2019s tyrosine kinase inhibitor, zanubrutinib","volume":"14","author":"Tam","year":"2021","journal-title":"Expert. Rev. Clin. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1182\/blood-2021-148544","article-title":"Phase 2 Study of Zanubrutinib in BTK Inhibitor-Intolerant Patients (Pts) with Relapsed\/Refractory B-Cell Malignancies","volume":"138","author":"Shadman","year":"2021","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1056\/NEJMoa2211582","article-title":"Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia","volume":"388","author":"Brown","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7521","DOI":"10.1200\/JCO.2022.40.16_suppl.7521","article-title":"ASPEN: Long-term follow-up results of a phase 3 randomized trial of zanubrutinib (ZANU) versus ibrutinib (IBR) in patients with Waldenstr\u00f6m macroglobulinemia (WM)","volume":"40","author":"Tam","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3441","DOI":"10.1200\/JCO.21.01210","article-title":"Acalabrutinib Versus Ibrutinib in Previously Treated Chronic Lymphocytic Leukemia: Results of the First Randomized Phase III Trial","volume":"39","author":"Byrd","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_32","unstructured":"National Comprehensive Cancer Network (2022, December 23). Chronic lymphocytic Leukemia\/Small Lymphocytic Lymphoma V1.2023. Available online: https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/cll.pdf."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1182\/blood-2022-158768","article-title":"The Impact of Drug Interactions on Outcomes in Ibrutinib-Treated Patients with Chronic Lymphocytic Leukemia in Routine Clinical Care: A Population-Based Cohort Study","volume":"140","author":"Hoang","year":"2022","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"711943","DOI":"10.3389\/fgene.2021.711943","article-title":"CYP3A4(\u2217)22 Genotyping in Clinical Practice: Ready for Implementation?","volume":"12","author":"Mulder","year":"2021","journal-title":"Front. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4365","DOI":"10.1182\/blood-2021-146610","article-title":"New Acalabrutinib Formulation Enables Co-Administration with Proton Pump Inhibitors and Dosing in Patients Unable to Swallow Capsules (ELEVATE-PLUS)","volume":"138","author":"Sharma","year":"2021","journal-title":"Blood"},{"key":"ref_36","unstructured":"(2022, December 23). Canadian Institute for Health Information. Drug Use among Seniors in Canada. Available online: https:\/\/secure.cihi.ca\/estore\/productFamily.htm?pf=PFC3729&lang=en&media=0."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1056\/NEJMoa1306220","article-title":"Targeting BTK with Ibrutinib in Relapsed or Refractory Mantle-Cell Lymphoma","volume":"369","author":"Wang","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1182\/bloodadvances.2021005621","article-title":"Pooled safety analysis of zanubrutinib monotherapy in patients with B-cell malignancies","volume":"6","author":"Tam","year":"2022","journal-title":"Blood Adv."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1182\/blood.2020006844","article-title":"A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenstr\u00f6m macroglobulinemia: The ASPEN study","volume":"136","author":"Tam","year":"2020","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"874","DOI":"10.3324\/haematol.2017.182907","article-title":"Toxicities and outcomes of 616 ibrutinib-treated patients in the United States: A real-world analysis","volume":"103","author":"Mato","year":"2018","journal-title":"Haematologica"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1182\/bloodadvances.2018030007","article-title":"Acalabrutinib monotherapy in patients with chronic lymphocytic leukemia who are intolerant to ibrutinib","volume":"3","author":"Awan","year":"2019","journal-title":"Blood Adv."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e35","DOI":"10.1016\/S2352-3026(22)00320-9","article-title":"Zanubrutinib in patients with previously treated B-cell malignancies intolerant of previous Bruton tyrosine kinase inhibitors in the USA: A phase 2, open-label, single-arm study","volume":"10","author":"Shadman","year":"2023","journal-title":"Lancet Haematol."},{"key":"ref_43","unstructured":"(2023, January 16). Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. National Cancer Institute, Available online: https:\/\/ctep.cancer.gov\/protocoldevelopment\/electronic_applications\/ctc.htm."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"630942","DOI":"10.3389\/fcell.2021.630942","article-title":"Comparative Analysis of BTK Inhibitors and Mechanisms Underlying Adverse Effects","volume":"9","author":"Zain","year":"2021","journal-title":"Front. Cell. Dev. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1016\/j.clml.2018.06.016","article-title":"Safety Analysis of Four Randomized Controlled Studies of Ibrutinib in Patients With Chronic Lymphocytic Leukemia\/Small Lymphocytic Lymphoma or Mantle Cell Lymphoma","volume":"18","author":"Hillmen","year":"2018","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1002\/ajh.25638","article-title":"Final analysis from RESONATE: Up to six years of follow-up on ibrutinib in patients with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma","volume":"94","author":"Munir","year":"2019","journal-title":"Am. J. Hematol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/s41375-019-0602-x","article-title":"Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL\/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study","volume":"34","author":"Burger","year":"2020","journal-title":"Leukemia"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1056\/NEJMoa1812836","article-title":"Ibrutinib Regimens versus Chemoimmunotherapy in Older Patients with Untreated CLL","volume":"379","author":"Woyach","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"8024","DOI":"10.1200\/JCO.2020.38.15_suppl.8024","article-title":"Acalabrutinib in treatment-na\u00efve chronic lymphocytic leukemia: Mature results from phase II study demonstrating durable remissions and long-term tolerability","volume":"38","author":"Byrd","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1182\/blood-2015-03-635326","article-title":"Long-term follow-up of MCL patients treated with single-agent ibrutinib: Updated safety and efficacy results","volume":"126","author":"Wang","year":"2015","journal-title":"Blood"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1016\/S0140-6736(20)30262-2","article-title":"Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): A randomised, controlled, phase 3 trial","volume":"395","author":"Sharman","year":"2020","journal-title":"Lancet"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2849","DOI":"10.1200\/JCO.19.03355","article-title":"ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia","volume":"38","author":"Ghia","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3918","DOI":"10.1158\/1078-0432.CCR-19-2856","article-title":"Ibrutinib Treatment for First-Line and Relapsed\/Refractory Chronic Lymphocytic Leukemia: Final Analysis of the Pivotal Phase Ib\/II PCYC-1102 Study","volume":"26","author":"Byrd","year":"2020","journal-title":"Clin. Cancer. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1182\/blood.2018884940","article-title":"Acalabrutinib monotherapy in patients with relapsed\/refractory chronic lymphocytic leukemia: Updated phase 2 results","volume":"135","author":"Byrd","year":"2020","journal-title":"Blood"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e112","DOI":"10.1016\/S2352-3026(19)30210-8","article-title":"Acalabrutinib monotherapy in patients with Waldenstr\u00f6m macroglobulinemia: A single-arm, multicentre, phase 2 study","volume":"7","author":"Owen","year":"2020","journal-title":"Lancet Haematol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1182\/blood-2018-11-846808","article-title":"How I manage ibrutinib intolerance and complications in patients with chronic lymphocytic leukemia","volume":"133","author":"Stephens","year":"2019","journal-title":"Blood"},{"key":"ref_57","unstructured":"Cancer Care Ontario (2022, December 29). Symptom Management Guide-to-Practice: Bowel Care. Available online: https:\/\/www.cancercareontario.ca\/en\/symptom-management\/3151."},{"key":"ref_58","unstructured":"National Health Service England (2022, December 29). Management of Systemic Anticancer Therapy Induced Diarrhoea in Adult Patients v2.3, Available online: https:\/\/wmcanceralliance.nhs.uk\/component\/rsfiles\/files?folder=Clinical%2BGuidelines%2Band%2BPathways%252FSACT&Itemid=236."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1111\/bjh.14302","article-title":"Ibrutinib-associated rash: A single-centre experience of clinicopathological features and management","volume":"180","author":"Iberri","year":"2018","journal-title":"Br. J. Haematol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"645","DOI":"10.3747\/co.27.6795","article-title":"Bruton Tyrosine Kinase Inhibitors for the Frontline Treatment of Chronic Lymphocytic Leukemia","volume":"27","author":"Banerji","year":"2020","journal-title":"Curr. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1007\/s40257-020-00535-x","article-title":"Dermatological Toxicities of Bruton\u2019s Tyrosine Kinase Inhibitors","volume":"21","author":"Sibaud","year":"2020","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_62","unstructured":"National Cancer Institute (2023, January 16). Skin and Nail Changes during Cancer Treatment 2019, Available online: https:\/\/www.cancer.gov\/about-cancer\/treatment\/side-effects\/skin-nail-changes."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1001\/jamadermatol.2016.0225","article-title":"Hair and Nail Changes During Long-term Therapy With Ibrutinib for Chronic Lymphocytic Leukemia","volume":"152","author":"Bitar","year":"2016","journal-title":"JAMA Dermatol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.3324\/haematol.2018.192328","article-title":"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","volume":"103","author":"Barr","year":"2018","journal-title":"Haematologica"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.clml.2020.02.001","article-title":"Ibrutinib-associated Arthralgias\/Myalgias in Patients With Chronic Lymphocytic Leukemia: Incidence and Impact on Clinical Outcomes","volume":"20","author":"Rhodes","year":"2020","journal-title":"Clin. Lymphoma. Myeloma. Leuk."},{"key":"ref_66","first-page":"1","article-title":"BTK inhibitors approved in Canada for CLL: Strategies for adverse event management","volume":"31","author":"Dunse","year":"2021","journal-title":"Can. Oncol. Nurs. J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1188\/20.CJON.392-398","article-title":"Acalabrutinib: Managing Adverse Events and Improving Adherence in Patients With Mantle Cell Lymphoma","volume":"24","author":"Badillo","year":"2020","journal-title":"Clin. J. Oncol. Nurs."},{"key":"ref_68","unstructured":"Howell, D., Keshavarz, H., Broadfield, L., Hack, T., Hamel, M., Harth, T., Jones, J., McLeod, D., Olson, K., and Phan, S. (2022, December 29). A Pan Canadian Practice Guideline for Screening, Assessment, and Management of Cancer-Related Fatigue in Adults: Version 2-2015. Available online: https:\/\/www.cancercareontario.ca\/en\/symptom-management\/3991."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1182\/hematology.2020000118","article-title":"Managing toxicities of Bruton tyrosine kinase inhibitors","volume":"2020","author":"Lipsky","year":"2020","journal-title":"Hematology"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3991","DOI":"10.1182\/blood-2014-06-583294","article-title":"Ibrutinib treatment affects collagen and von Willebrand factor-dependent platelet functions","volume":"124","author":"Levade","year":"2014","journal-title":"Blood"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.3324\/haematol.2017.164103","article-title":"Incidence and management of toxicity associated with ibrutinib and idelalisib: A practical approach","volume":"102","author":"Koopmans","year":"2017","journal-title":"Haematologica"},{"key":"ref_72","unstructured":"National Cancer Institute (2022, December 29). Bleeding and Bruising (Thrombocytopenia) and Cancer Treatment, Available online: https:\/\/www.cancer.gov\/about-cancer\/treatment\/side-effects\/bleeding-bruising."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.3324\/haematol.2015.126672","article-title":"Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib","volume":"100","author":"Lipsky","year":"2015","journal-title":"Haematologica"},{"key":"ref_74","unstructured":"Johnson, A., and Burns, B. (2020). StatPearls, StatPearls Publishing."},{"key":"ref_75","unstructured":"Taghavi, S., and Askari, R. (2022, October 04). Hypovolemic Shock, StatPearls, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK513297\/."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.clml.2018.07.287","article-title":"Risk of Major Bleeding with Ibrutinib","volume":"18","author":"Mock","year":"2018","journal-title":"Clin. Lymphoma. Myeloma. Leuk."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1038\/leu.2014.247","article-title":"Ibrutinib inhibits collagen-mediated but not ADP-mediated platelet aggregation","volume":"29","author":"Kamel","year":"2015","journal-title":"Leukemia"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1111\/jth.13651","article-title":"Ibrutinib-associated bleeding: Pathogenesis, management and risk reduction strategies","volume":"15","author":"Shatzel","year":"2017","journal-title":"J. Thromb. Haemost."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1182\/bloodadvances.2018028761","article-title":"Long-term safety of single-agent ibrutinib in patients with chronic lymphocytic leukemia in 3 pivotal studies","volume":"3","author":"Coutre","year":"2019","journal-title":"Blood Adv."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1182\/blood-2020-140577","article-title":"Real-World Outcomes of Patients Treated with Single-Agent Ibrutinib for Chronic Lymphocytic Leukemia\/Small Lymphocytic Lymphoma (CLL\/SLL): A Systematic Review and Meta-Analysis","volume":"136","author":"Cheung","year":"2020","journal-title":"Blood"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1182\/blood.2019000840","article-title":"Hypertension and incident cardiovascular events following ibrutinib initiation","volume":"134","author":"Dickerson","year":"2019","journal-title":"Blood"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s13045-022-01302-7","article-title":"Hypertension and incident cardiovascular events after next-generation BTKi therapy initiation","volume":"15","author":"Chen","year":"2022","journal-title":"J. Hematol. Amp. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s11912-021-01102-1","article-title":"Bruton\u2019s tyrosine kinase Inhibitors and Cardiotoxicity: More Than Just Atrial Fibrillation","volume":"23","author":"Sestier","year":"2021","journal-title":"Curr. Oncol. Rep."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"(2015). A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N. Engl. J. Med., 373, 2103\u20132116.","DOI":"10.1056\/NEJMoa1511939"},{"key":"ref_85","unstructured":"American Heart Association (2022, December 29). What is high blood pressure?. Available online: www.heart.org\/-\/media\/files\/health-topics\/answers-by-heart\/what-is-high-blood-pressure.pdf."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1056\/NEJMoa1509388","article-title":"Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia","volume":"373","author":"Burger","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1056\/NEJMoa1817073","article-title":"Ibrutinib\u2013Rituximab or Chemoimmunotherapy for Chronic Lymphocytic Leukemia","volume":"381","author":"Shanafelt","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S1470-2045(18)30788-5","article-title":"Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): A multicentre, randomised, open-label, phase 3 trial","volume":"20","author":"Moreno","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s13045-018-0626-0","article-title":"Predictors of atrial fibrillation in ibrutinib-treated CLL patients: A prospective study","volume":"11","author":"Reda","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1080\/10428194.2016.1257795","article-title":"Atrial fibrillation in patients with chronic lymphocytic leukemia (CLL)","volume":"58","author":"Shanafelt","year":"2016","journal-title":"Leuk Lymphoma"},{"key":"ref_91","unstructured":"American Heart Association (2023, January 16). What are the symptoms of atrial fibrillation (Afib or AF)?. Available online: https:\/\/www.heart.org\/en\/health-topics\/atrial-fibrillation\/what-are-the-symptoms-of-atrial-fibrillation-afib-or-af."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1161\/CIRCULATIONAHA.111.060061","article-title":"Use of the CHA2DS2-VASc and HAS-BLED Scores to Aid Decision Making for Thromboprophylaxis in Nonvalvular Atrial Fibrillation","volume":"126","author":"Lane","year":"2012","journal-title":"Circulation"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.jaccao.2020.11.016","article-title":"How to Manage Atrial Fibrillation Secondary to Ibrutinib","volume":"3","author":"Essa","year":"2021","journal-title":"JACC CardioOncol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.1080\/10428194.2017.1315115","article-title":"Practical recommendations for the choice of anticoagulants in the management of patients with atrial fibrillation on ibrutinib","volume":"58","author":"Chai","year":"2017","journal-title":"Leuk. Lymphoma"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.3324\/haematol.2021.278901","article-title":"Cardiovascular adverse events in patients with chronic lymphocytic leukemia receiving acalabrutinib monotherapy: Pooled analysis of 762 patients","volume":"107","author":"Brown","year":"2021","journal-title":"Haematologica"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1182\/blood-2016-10-742437","article-title":"Ventricular arrhythmias and sudden death in patients taking ibrutinib","volume":"129","author":"Lampson","year":"2017","journal-title":"Blood"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.1182\/blood.2022016953","article-title":"Ventricular arrhythmias and sudden death events following acalabrutinib initiation","volume":"140","author":"Bhat","year":"2022","journal-title":"Blood"},{"key":"ref_98","unstructured":"Government of Canada: Recalls and safety alerts (2022, December 30). Health professional risk communication: IMBRUVICA (ibrutinib)-Risk of Serious and Fatal Cardiac Arrhythmias or Cardiac Failure, Available online: https:\/\/recalls-rappels.canada.ca\/en\/alert-recall\/imbruvica-ibrutinib-risk-serious-and-fatal-cardiac-arrhythmias-or-cardiac-failure."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.jacep.2016.07.004","article-title":"Ibrutinib, an Approved Tyrosine Kinase Inhibitor as a Potential Cause of Recurrent Polymorphic Ventricular Tachycardia","volume":"2","year":"2016","journal-title":"JACC Clin. Electrophysiol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1002\/ccr3.719","article-title":"A case of new-onset cardiomyopathy and ventricular tachycardia in a patient receiving ibrutinib for relapsed mantle cell lymphoma","volume":"4","author":"Wallace","year":"2016","journal-title":"Clin. Case. Rep."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.jacc.2018.06.002","article-title":"Ventricular Arrhythmias Following Ibrutinib Initiation for Lymphoid Malignancies","volume":"72","author":"Guha","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1080\/10428194.2018.1512710","article-title":"Characterizing the kinetics of lymphocytosis in patients with chronic lymphocytic leukemia treated with single-agent ibrutinib","volume":"60","author":"Barrientos","year":"2019","journal-title":"Leuk. Amp. Lymphoma."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.1038\/leu.2014.122","article-title":"Ibrutinib-induced lymphocytosis in patients with chronic lymphocytic leukemia: Correlative analyses from a phase II study","volume":"28","author":"Herman","year":"2014","journal-title":"Leukemia"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1007\/s00277-016-2917-2","article-title":"Severe hepatitis B virus reactivation related to ibrutinib monotherapy","volume":"96","author":"Herishanu","year":"2017","journal-title":"Ann. Hematol."},{"key":"ref_105","first-page":"208","article-title":"Hepatitis B Virus Reactivation Under \u0130brutinib Treatment in a Patient With Chronic Lymphocytic Leukemia","volume":"37","author":"Ertek","year":"2020","journal-title":"Turk. J. Hematol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.3324\/haematol.2021.280325","article-title":"Risk of hepatitis B virus reactivation in chronic lymphocytic leukemia patients receiving ibrutinib with or without antiviral prophylaxis. A retrospective multicentric GIMEMA study","volume":"107","author":"Innocenti","year":"2022","journal-title":"Haematologica"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e307","DOI":"10.1097\/HS9.0000000000000307","article-title":"Rare but Serious: Ibrutinib Induced Liver Failure","volume":"3","author":"Kleijwegt","year":"2019","journal-title":"Hemasphere"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Atallah, E., Wijayasiri, P., Cianci, N., Abdullah, K., Mukherjee, A., and Aithal, G.P. (2021). Zanubrutinib-induced liver injury: A case report and literature review. BMC Gastroenterol., 21.","DOI":"10.1186\/s12876-021-01825-2"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"3197","DOI":"10.1038\/s41375-020-0987-6","article-title":"Second cancer incidence in CLL patients receiving BTK inhibitors","volume":"34","author":"Bond","year":"2020","journal-title":"Leukemia"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.3109\/10428194.2014.957203","article-title":"Second cancers in patients with chronic lymphocytic leukemia who received frontline fludarabine, cyclophosphamide and rituximab therapy: Distribution and clinical outcomes","volume":"56","author":"Benjamini","year":"2015","journal-title":"Leuk. Amp. Lymphoma."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1200\/JCO.2008.17.5398","article-title":"Other Malignancies in Chronic Lymphocytic Leukemia\/Small Lymphocytic Lymphoma","volume":"27","author":"Tsimberidou","year":"2009","journal-title":"J. Clin. Oncol."}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/30\/4\/322\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:18:05Z","timestamp":1760123885000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/30\/4\/322"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,18]]},"references-count":111,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["curroncol30040322"],"URL":"https:\/\/doi.org\/10.3390\/curroncol30040322","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,18]]}}}