{"doi":"10.1002/hon.70096_552","title":"552 | BRUTON'S TYRONSINE KINASE INHIBITORS VERSUS VENETOCLAX IN CHRONIC LYMPHOCYTIC LEUKEMIA AND SMALL LYMPHOCYTIC LYMPHOMA: A RETROSPECTIVE REAL‐WORLD ANALYSIS.","abstract":"A. Zickar, R. Wan, J. Switchenko, S. Wyman, L. Sun, J. Koff, A. Chang, and J. Cohen equally contributing author. Introduction: Limited data are available comparing the two primary oral approaches to previously untreated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We evaluated outcomes for all patients treated with covalent Bruton’s tyrosine kinase inhibitors (BTKi) or a venetoclax-based regimen at our center and assessed the impact of patient- and disease-related characteristics on response to treatment, safety, progression-free survival (PFS) and overall survival (OS). Methods: Electronic health records of patients with CLL/SLL who received frontline BTKi (ibrutinib, acalabrutinib, or zanubrutinib) or venetoclax between 2013 and 2025 were reviewed. Individuals on the triplet therapy trial were excluded. Data collected included disease-related genetic risk factors at treatment initiation, adverse events, response to treatment, time to disease progression or discontinuation of therapy, and survival. We assessed differences in PFS, OS, baseline prognostic markers, and side effects between the two approaches. PFS and OS were defined as time from initiation of therapy to progression or death (PFS) or death from any cause (OS) with living patients censored at the time of last follow-up. Survival distributions were estimated using the Kaplan-Meier method and compared using log-rank tests. Cox proportional hazards models were fit for PFS and OS as a function of patient characteristics. Results: Of 382 patients (median age 65.4 years), 197 patients received a BTKi and 71 received venetoclax. The populations were predominantly Caucasian (61.5%), male (62.8%), immunoglobulin heavy-chain variable region gene (IGHV) unmutated (39.1%), and del(17p) unmutated (77.7%). There was no significant difference between the groups with regards to OS (HR 0.52, 95% CI: 0.18–1.49, p = 0.22) or PFS (HR 0.80, 95% CI: 0.40–1.60, p = 0.53; Figure 1a,b). This was consistent when stratified by presence of IGHV mutation (HR 0.57, CI: 0.32–1.04, p = 0.068) and del(17p) (HR 1.40, CI: 0.86–2.27, p = 0.17). Peripheral neuropathy incidence was 2.0% in the BTKi group and 2.8% in the venetoclax group. Arrhythmias were reported at 9.1% for patients on BTKi and 1.4% for those on venetoclax. Anemia, leukopenia, and thrombocytopenia were reported in the BTKi group (31.5%, 10.7%, and 26.4%, respectively) and the venetoclax group (32.4%, 45.1%, and 35.2%, respectively). Conclusions: In our dataset, PFS and OS were similar across CLL/SLL patients receiving BTKi and venetoclax-based induction therapies, with no significant impact based on therapy selection. Side effects were comparable between the two regimens, with similar incidence of arrythmia, cytopenia, and neuropathy. The prolonged PFS and OS achieved by both regimens support the selection of treatment based on patient-specific factors and preferences in the front-line setting. Keywords: diagnostic and prognostic biomarkers; chronic lymphocytic leukemia (CLL); molecular targeted therapies Potential sources of conflict of interest: J. Koff Consultant or advisory role: Consulting fees from AbbVie, BeiGene, Pierre Fabre Other remuneration: Research funded by grants from NIH/NCI, Leukemia Lymphoma Society; Clinical trials and/or research grants from Oncternal Therapeutics, Viracta Therapeutics A. Chang Consultant or advisory role: Consultant for AbbVie and AstraZeneca Other remuneration: Research Funding from AbbVie J. Cohen Consultant or advisory role: Advisor for Beigene, AstraZeneca Other remuneration: Research funding from Nurix, AstraZeneca","journal":"Hematological Oncology","year":2025,"id":568501,"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":0.9522,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1472761,"name":"Rui Wan","orcid":"0000-0002-7177-7736","position":1,"is_corresponding":false},{"id":305854,"name":"Jeffrey M. Switchenko","orcid":"0000-0002-5563-9325","position":2,"is_corresponding":false},{"id":273395,"name":"Stacia K. Wyman","orcid":"0000-0002-8937-8397","position":3,"is_corresponding":false},{"id":1472762,"name":"Krzysztof Simon","orcid":"0000-0002-8040-0412","position":4,"is_corresponding":false},{"id":1473321,"name":"Alexandra Palmer","orcid":null,"position":5,"is_corresponding":false},{"id":1153113,"name":"Liping Sun","orcid":"0000-0003-3637-0305","position":6,"is_corresponding":false},{"id":1473322,"name":"Hafsa Bhatty","orcid":null,"position":7,"is_corresponding":false},{"id":680215,"name":"Jean L. Koff","orcid":"0000-0003-4414-0489","position":8,"is_corresponding":false},{"id":680214,"name":"Andrés Chang","orcid":"0000-0001-6679-9060","position":9,"is_corresponding":false},{"id":262217,"name":"Jonathon B. Cohen","orcid":"0000-0002-2723-6481","position":10,"is_corresponding":false},{"id":1473320,"name":"A. Zickar","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:56:52.212268Z","pmid":null,"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":[]}