{"doi":"10.1002/ajh.26595","title":"<i>TP53</i>‐altered chronic lymphocytic leukemia treated with firstline Bruton's tyrosine kinase inhibitor‐based therapy: A retrospective analysis","abstract":"Long-term follow up of prospective studies has shown that continuous Bruton's tyrosine kinase inhibitor (BTKi) therapy leads to durable remissions in previously untreated patients with TP53-altered chronic lymphocytic leukemia (CLL); however, it is unknown how variant allele frequency (VAF) of TP53 mutation (TP53-m) or percentage of cells with deletion of chromosome 17p [del(17p)] influences efficacy of firstline BTKi. We performed a retrospective analysis of 130 patients with CLL with baseline del(17p) and/or TP53-m treated with BTKi with or without the BCL2 inhibitor venetoclax (VEN) and with or without CD20 antibody in the firstline setting. A total of 104/130 (80%) patients had del(17p). TP53-m was noted in 89/110 (81%) patients tested; there were 101 unique TP53-m with an available VAF. The 4-year progression-free survival (PFS) and overall survival (OS) rates were 72.9% and 83.6%. No baseline characteristics including IGHV mutation status and number of TP53 alterations were associated with significant differences in PFS or OS, though a trend toward shorter PFS with increasing karyotypic complexity (hazard ratio 1.08, p = .066) was observed. Del(17p) was identified in <25% of cells in 26/104 (25%) of patients, and 28/101 (28%) of TP53-m were low-burden with a VAF of <10%; outcomes of these patients were similar to those with high-burden lesions. This study suggests that low-burden TP53 alterations should not be ignored when assessing genomic risk in CLL in the era of targeted therapy.","journal":"American Journal of Hematology","year":2022,"id":270143,"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":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9576,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":934437,"name":"Raamis Khwaja","orcid":null,"position":1,"is_corresponding":false},{"id":250530,"name":"Rashmi Kanagal‐Shamanna","orcid":"0000-0001-7829-5249","position":2,"is_corresponding":false},{"id":627516,"name":"Guilin Tang","orcid":"0000-0002-9482-4806","position":3,"is_corresponding":false},{"id":232849,"name":"Jan A. Burger","orcid":"0000-0002-6177-7572","position":4,"is_corresponding":false},{"id":104765,"name":"Philip A. Thompson","orcid":"0000-0003-2086-6031","position":5,"is_corresponding":false},{"id":232855,"name":"Alessandra Ferrajoli","orcid":"0000-0001-9547-4193","position":6,"is_corresponding":false},{"id":232851,"name":"Zeev Estrov","orcid":"0000-0002-1623-3613","position":7,"is_corresponding":false},{"id":232853,"name":"Koji Sasaki","orcid":"0000-0002-9140-0610","position":8,"is_corresponding":false},{"id":692294,"name":"Deepa Sampath","orcid":"0000-0002-4366-8436","position":9,"is_corresponding":false},{"id":293088,"name":"Xuemei Wang","orcid":"0000-0002-3516-0966","position":10,"is_corresponding":false},{"id":109598,"name":"Hagop M. Kantarjian","orcid":"0000-0002-1908-3307","position":11,"is_corresponding":false},{"id":104777,"name":"Michael J. Keating","orcid":"0000-0002-9121-6450","position":12,"is_corresponding":false},{"id":104776,"name":"William G. Wierda","orcid":"0000-0002-7357-270X","position":13,"is_corresponding":false},{"id":232850,"name":"Nitin Jain","orcid":"0000-0003-0114-8384","position":14,"is_corresponding":false},{"id":933073,"name":"Hua‐Jay J. Cherng","orcid":"0000-0002-8266-8447","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T00:27:26.772098Z","pmid":"35567779","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":[]}