{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T12:10:33Z","timestamp":1772539833340,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Ibrutinib has revolutionized the treatment of chronic lymphocytic leukemia but has off-target side effects, most notably cardiac. In order to evaluate the efficacy and toxicity of ibrutinib treatment, risk factors for adverse outcomes and the influence of pretreatment cardiologic evaluation, KroHem collected data on Croatian patients with chronic lymphocytic leukemia treated with this drug. Methods: This is a retrospective survey performed in order to analyze the efficacy and toxicity of ibrutinib in a real-life setting. Patients starting therapy with ibrutinib for chronic lymphocytic leukemia between the time the drug became reimbursable in 2015 and 31 December 2021 were included, irrespective of treatment line. Results: We identified 436 patients fulfilling entry criteria; 404 (92.7%) responded to treatment. Cardiovascular side effects occurred in 25.0% of patients and hemorrhagic in 15.6%. The dose of ibrutinib was permanently reduced in 22.2% of patients. Median follow-up of the cohort was 29 months (IQR 18\u201341 months), estimated median overall survival 75 months (IQR 36 months\u2013not reached), progression-free survival 54 months (IQR 24\u201381 months) and time on ibrutinib treatment 44 months (IQR 14\u201378 months). Factors significantly related to overall survival in multivariate analysis were stage, treatment line and age. Factors significantly related to progression-free survival in multivariate analysis were treatment line, age and pretreatment history or ECG finding of cardiac arrhythmia. Factors significantly related to time on ibrutinib treatment in multivariate analysis were age, pretreatment history or ECG finding of cardiac arrhythmia, and permanent dose reduction for toxicity. Sex, FISH and the presence of arterial hypertension were not independently significantly related to any of these outcomes. Pretreatment cardiologic consultation did not improve time on ibrutinib therapy, progression-free survival, overall survival, risk of stopping treatment due to cardiovascular side effects or risk of cardiovascular or sudden death, neither in the whole cohort nor in the subgroup of patients with and without pretreatment cardiac arrhythmia. Conclusions: Our analysis confirms the efficacy and tolerability of ibrutinib for the treatment of chronic lymphocytic leukemia. Patients older than 75 do significantly less well. Routine pretreatment cardiologic consultation does not improve outcomes and should not be considered part of standard pretreatment assessment without additional proof of its usefulness. Future investigations should aim at identifying predictive factors, mechanisms, and preventive strategies for reducing cardiotoxicity in chronic lymphocytic leukemia patients taking Bruton tyrosine kinase inhibitors.<\/jats:p>","DOI":"10.3390\/cancers17142302","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T15:36:58Z","timestamp":1752161818000},"page":"2302","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Efficacy, Toxicity and Effect of Pretreatment Cardiologic Consultation on Outcomes of Ibrutinib Therapy for Chronic Lymphocytic Leukemia\u2014A KroHem Study"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5234-9464","authenticated-orcid":false,"given":"Inga","family":"Mandac Smoljanovi\u0107","sequence":"first","affiliation":[{"name":"University Hospital Merkur, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6175-4277","authenticated-orcid":false,"given":"Igor","family":"Aurer","sequence":"additional","affiliation":[{"name":"University Hospital Centre Zagreb, 10000 Zagreb, Croatia"},{"name":"School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikola","family":"Bulj","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"University Hospital Centre Sisters of Mercy, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Dreta","sequence":"additional","affiliation":[{"name":"University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonija","family":"Miljak","sequence":"additional","affiliation":[{"name":"University Hospital Centre Split, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fran","family":"Petri\u010devi\u0107","sequence":"additional","affiliation":[{"name":"University Hospital Centre Sisters of Mercy, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marija","family":"Ivi\u0107","sequence":"additional","affiliation":[{"name":"University Hospital Dubrava, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Ba\u0161i\u0107-Kinda","sequence":"additional","affiliation":[{"name":"University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viktor","family":"Zatezalo","sequence":"additional","affiliation":[{"name":"University Hospital Merkur, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanja","family":"Maduni\u0107","sequence":"additional","affiliation":[{"name":"University Hospital Centre Split, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dubravka","family":"\u010car\u017eavec","sequence":"additional","affiliation":[{"name":"University Hospital Centre Sisters of Mercy, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasminka","family":"Sin\u010di\u0107-Petri\u010devi\u0107","sequence":"additional","affiliation":[{"name":"University Hospital Centre Osijek, 31000 Osijek, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dragana","family":"Grohovac","sequence":"additional","affiliation":[{"name":"University Hospital Centre Rijeka, 51000 Rijeka, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ozren","family":"Jak\u0161i\u0107","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"University Hospital Dubrava, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan","family":"Kre\u010dak","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Rijeka, 51000 Rijeka, Croatia"},{"name":"General Hospital \u0160ibenik, 22000 \u0160ibenik, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Mori\u0107-Peri\u0107","sequence":"additional","affiliation":[{"name":"General Hospital Zadar, 23000 Zadar, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo\u017eena","family":"Coha","sequence":"additional","affiliation":[{"name":"General Hospital Dr. Josip Ben\u010devi\u0107, 35000 Slavonski Brod, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Berne\u0161","sequence":"additional","affiliation":[{"name":"General Hospital Pula, 52100 Pula, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neno","family":"\u017divkovi\u0107","sequence":"additional","affiliation":[{"name":"University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vlatko","family":"Pej\u0161a","sequence":"additional","affiliation":[{"name":"University Hospital Dubrava, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13045-022-01353-w","article-title":"BTK inhibitors in the treatment of hematological malignancies and inflammatory diseases: Mechanisms and clinical studies","volume":"15","author":"Alu","year":"2022","journal-title":"J. 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