{"doi":"10.1056/evidoa2200006","title":"Fixed-Duration Ibrutinib-Venetoclax in Patients with Chronic Lymphocytic Leukemia and Comorbidities","abstract":null,"journal":"NEJM Evidence","year":2022,"id":594760,"datarank":0.8182981673036553,"base_score":5.455321115357702,"endowment":5.455321115357702,"self_citation_contribution":0.8182981673036553,"citation_network_contribution":0.0,"self_endowment_contribution":0.8182981673036553,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":233,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":242772,"name":"Carolyn Owen","orcid":"0000-0003-4110-1708","position":1,"is_corresponding":false},{"id":535516,"name":"Carol Moreno","orcid":"0000-0003-3275-0271","position":2,"is_corresponding":false},{"id":1363075,"name":"George Follows","orcid":"0000-0002-8489-0762","position":3,"is_corresponding":false},{"id":234680,"name":"Talha Munir","orcid":null,"position":4,"is_corresponding":false},{"id":1522692,"name":"Mark-David Levin","orcid":null,"position":5,"is_corresponding":false},{"id":122531,"name":"Ohad Benjamini","orcid":null,"position":6,"is_corresponding":false},{"id":686954,"name":"Ann Janssens","orcid":"0000-0002-1812-412X","position":7,"is_corresponding":false},{"id":1522693,"name":"Anders Osterborg","orcid":null,"position":8,"is_corresponding":false},{"id":242773,"name":"Tadeusz Robak","orcid":"0000-0002-3411-6357","position":9,"is_corresponding":false},{"id":1522694,"name":"Martin Simkovic","orcid":null,"position":10,"is_corresponding":false},{"id":1522695,"name":"Don Stevens","orcid":null,"position":11,"is_corresponding":false},{"id":1522696,"name":"Sergey Voloshin","orcid":null,"position":12,"is_corresponding":false},{"id":1522697,"name":"Vladimir Vorobyev","orcid":null,"position":13,"is_corresponding":false},{"id":1522698,"name":"Loic Ysebaert","orcid":null,"position":14,"is_corresponding":false},{"id":826638,"name":"Rui Qin","orcid":"0000-0001-5822-3985","position":15,"is_corresponding":false},{"id":1382668,"name":"Andrew J. Steele","orcid":"0000-0003-0667-1596","position":16,"is_corresponding":false},{"id":1522699,"name":"Natasha Schuier","orcid":null,"position":17,"is_corresponding":false},{"id":1522700,"name":"Kurt Baeten","orcid":null,"position":18,"is_corresponding":false},{"id":1522701,"name":"Donne Bennett Caces","orcid":null,"position":19,"is_corresponding":false},{"id":1522702,"name":"Carsten U. Niemann","orcid":null,"position":20,"is_corresponding":false},{"id":242765,"name":"Arnon P. Kater","orcid":"0000-0003-3190-1891","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Fixed-Duration Ibrutinib-Venetoclax in Patients with Chronic Lymphocytic Leukemia and Comorbidities","abstract":"BACKGROUND: GLOW is a phase 3 trial evaluating the efficacy and safety of ibrutinib-venetoclax in older patients and/or those with comorbidities with previously untreated chronic lymphocytic leukemia (CLL). METHODS: We randomly assigned (1:1) patients 65 years of age or older or those 18 to 64 years of age who also had a Cumulative Illness Rating Scale (CIRS) score greater than 6 (CIRS scores range from 0 to 56, with higher scores indicating more impaired function of organ systems) or creatinine clearance of less than 70 ml/min, to ibrutinib-venetoclax (3 cycles ibrutinib lead-in, then 12 cycles ibrutinib-venetoclax) or chlorambucil-obinutuzumab (6 cycles). The primary end point was progression-free survival (PFS) assessed by an independent review committee. Secondary end points included undetectable minimal residual disease (uMRD), response rates, and safety. RESULTS: This study enrolled 211 patients, with 106 randomly assigned to ibrutinib-venetoclax and 105 to chlorambucil-obinutuzumab. With a median follow-up of 27.7 months, there were 22 PFS events for ibrutinib-venetoclax and 67 events for chlorambucil-obinutuzumab. PFS was significantly longer for ibrutinib-venetoclax than for chlorambucil-obinutuzumab (hazard ratio, 0.216; 95% confidence interval [CI], 0.131 to 0.357; P<0.001). The improvement in PFS with ibrutinib-venetoclax was consistent across predefined subgroups, including patients 65 years of age or older or with a CIRS score greater than 6. The best uMRD rate in bone marrow by next-generation sequencing was significantly higher for ibrutinib-venetoclax (55.7%) than for chlorambucil-obinutuzumab (21.0%; P<0.001). The proportion of patients with sustained uMRD in peripheral blood from 3 to 12 months after end of treatment was 84.5% for ibrutinib-venetoclax and 29.3% for chlorambucil-obinutuzumab. Four patients treated with ibrutinib-venetoclax required subsequent therapy compared with 27 patients receiving chlorambucil-obinutuzumab (hazard ratio, 0.143; 95% CI, 0.050 to 0.410). Adverse events grade 3 or greater occurred for 80 (75.5%) and 73 (69.5%) patients receiving ibrutinib-venetoclax and chlorambucil-obinutuzumab, respectively, with neutropenia being most common in both arms (37 [34.9%] and 52 [49.5%]). There were 11 (10.4%) and 12 (11.4%) all-cause deaths in the ibrutinib-venetoclax and chlorambucil-obinutuzumab arms, respectively. CONCLUSIONS: Ibrutinib-venetoclax, an all-oral, once-daily, fixed-duration combination, demonstrated superior PFS and deeper and better sustained responses versus chlorambucil-obinutuzumab as first-line CLL treatment in older patients and/or those with comorbidities. (Funded by Janssen Research & Development, LLC, and Pharmacyclics; ClinicalTrials.gov number, NCT03462719.)","is_dataset_classified":null,"base_score":5.455321115357702,"endowment":5.455321115357702,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"38319255","pmcid":null,"openalex_id":"https://openalex.org/W4280503361","authors":[],"funders":[],"total_grants":0,"fwci":27.2927,"citation_percentile":0.99753222,"influential_citations":0,"citation_trend":[{"year":2022,"count":10},{"year":2023,"count":62},{"year":2024,"count":61},{"year":2025,"count":67},{"year":2026,"count":32}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://doi.org/10.1056/evidoa2200006","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/38319255","host_type":"repository"},{"url":"https://inserm.hal.science/inserm-04783087","host_type":"repository"}],"fields_of_study":["Chronic Lymphocytic Leukemia Research","Lymphoma Diagnosis and Treatment","Immunodeficiency and Autoimmune Disorders","Humans","Leukemia, Lymphocytic, Chronic, B-Cell","Aged","Male","Female","Middle Aged","Adenine","Piperidines","Adult","Comorbidity","Aged, 80 and over","Pyrimidines","Pyrazoles","Antineoplastic Combined Chemotherapy Protocols","Young Adult","Antineoplastic Agents"],"mesh_terms":["Adenine","Adult","Aged","Aged, 80 and over","Antineoplastic Agents","Antineoplastic Combined Chemotherapy Protocols","Female","Humans","Male","Middle Aged","Piperidines","Pyrazoles","Pyrimidines","Leukemia, Lymphocytic, Chronic, B-Cell","Comorbidity","Young Adult"],"keywords":["Ibrutinib","Venetoclax","Chlorambucil","Medicine","Obinutuzumab","Chronic lymphocytic leukemia","Internal medicine","Oncology","Adverse effect","Leukemia","Chemotherapy","Cyclophosphamide"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-27T15:29:29.854552Z","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":[]}