{"doi":"10.1111/bjh.19737","title":"Outcomes of Bruton tyrosine kinase inhibitors for chronic lymphocytic leukaemia in US veterans with severe renal dysfunction","abstract":"There are limited data to guide the use of Bruton tyrosine kinase inhibitors (BTKi) in patients who have renal dysfunction. Severe kidney disease was excluded from pivotal trials, and manufacturer labels of approved BTKi provide little guidance on the safety of their use in this population.1-3 Ibrutinib has low levels of renal excretion, but is associated with kidney injury and may worsen existing renal dysfunction.1, 4, 5 This US Veterans Health Administration (VHA) retrospective cohort study aims to evaluate the real-world outcomes of BTK inhibition in patients with chronic lymphocytic leukaemia (CLL) and concurrent severe renal impairment. We performed an electronic query of the VHA Corporate Data Warehouse to identify veterans with CLL and an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 while receiving treatment with a BTKi. Only patients with kidney dysfunction that persisted beyond 1 month were included. Retrospective chart review was conducted to collect data on patient characteristics, CLL therapies, and clinical outcomes. Fisher's exact and chi-square testing were utilized to evaluate categorical variables, logistic regression for binary outcomes and log-rank testing and Cox proportional hazards regression for time-to-event analyses. Our query identified 115 eligible patients who were treated with a BTKi between 1 January 2013 and 1 December 2022 (Table 1), with eight receiving more than one BTKi. These 115 veterans received their care across 68 VHA medical centres. The median duration of follow-up from the start of therapy was 26 months (range, 0.5–94). The cohort demographics were representative of the VHA population: median age was 74 years, 98% male and 68% non-Hispanic White. Thirty-nine patients (34%) progressed from none or only mild renal dysfunction to severe renal dysfunction (eGFR <30) at a median of 12.3 months from initiation of the BTK inhibitor (range, 0.3–72.6). The cause of worsening renal failure was unknown in 59% of patients, with only 7% attributed to the BTK inhibitor. Progressive renal dysfunction led to dose reduction in 5 (4%) patients and drug discontinuation in 5 (4%) patients. Twenty-one (18%) patients were on dialysis at the initiation of therapy, while an additional 16 (14%) became dialysis dependent during therapy. The BTKi prescribed were ibrutinib (n = 103), acalabrutinib (n = 18) and zanubrutinib (n = 3). Of the 124 BTKi prescribed, 64 (52%) were utilized as initial therapy, 42 (34%) as second line and 18 (14%) as third or later line. BTKi were started at the FDA label dose in 94 patients (76%), with the rest initiated at a reduced dose. Forty-six (37%) required a dose reduction during treatment, primarily due to drug toxicity (n = 37). Specifically, the most common reasons cited for dose reduction were cytopenias (n = 10) and failure to thrive (n = 6). Toxicity was the cause of discontinuation for 50% of the ibrutinib courses, 39% of acalabrutinib and 33% of zanubrutinib. The most common specific causes for discontinuation were infection (n = 15), bleeding (n = 10), arrhythmia (n = 9) and disease progression (n = 9). Ibrutinib had higher rates of new symptomatic tachyarrhythmias or stroke compared to acalabrutinib and zanubrutinib (16.5% vs. 0%, p = 0.045), while use of haemodialysis was not associated with increased rates of these cardiovascular events. Neither the BTK inhibitor choice nor haemodialysis was associated with an increased incidence of severe infections requiring hospitalization or intravenous antimicrobials. Among the 103 patients who received ibrutinib, the median duration of therapy (DoT) was 33.4 months, and the median overall survival (OS) was 49 months. The most common attributed causes of death were infection (n = 19), disease progression (n = 10) and renal failure (n = 10). In multivariable regression, factors that impacted DoT included subsequent dose reduction (HR 0.45, 95% CI 0.24–0.82), eGFR at initiation at BTK initiation (HR 0.98, 95% CI ","journal":"British Journal of Haematology","year":2024,"id":502733,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9538,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1352193,"name":"Clare Anderson","orcid":"0000-0002-5970-5799","position":1,"is_corresponding":false},{"id":1352194,"name":"Micaela R. Scobie","orcid":"0000-0002-9217-0562","position":2,"is_corresponding":false},{"id":273373,"name":"Thomas D. Rodgers","orcid":"0000-0002-8937-8231","position":3,"is_corresponding":false},{"id":736129,"name":"Michael J. Kelley","orcid":"0000-0001-9523-6080","position":4,"is_corresponding":false},{"id":1175729,"name":"Daphne R. Friedman","orcid":"0000-0002-2938-5704","position":5,"is_corresponding":false},{"id":354491,"name":"Chenyu Lin","orcid":"0000-0002-4542-4232","position":0,"is_corresponding":true}],"reference_count":3,"raw_metadata":null,"created_at":"2026-07-19T02:10:23.709105Z","pmid":"39209771","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}