{"doi":"10.1182/blood.2023020554","title":"Ibrutinib-based therapy reinvigorates CD8+ T cells compared to chemoimmunotherapy: immune monitoring from the E1912 trial","abstract":"ABSTRACT: Bruton tyrosine kinase inhibitors (BTKis) that target B-cell receptor signaling have led to a paradigm shift in chronic lymphocytic leukemia (CLL) treatment. BTKis have been shown to reduce abnormally high CLL-associated T-cell counts and the expression of immune checkpoint receptors concomitantly with tumor reduction. However, the impact of BTKi therapy on T-cell function has not been fully characterized. Here, we performed longitudinal immunophenotypic and functional analysis of pretreatment and on-treatment (6 and 12 months) peripheral blood samples from patients in the phase 3 E1912 trial comparing ibrutinib-rituximab with fludarabine, cyclophosphamide, and rituximab (FCR). Intriguingly, we report that despite reduced overall T-cell counts; higher numbers of T cells, including effector CD8+ subsets at baseline and at the 6-month time point, associated with no infections; and favorable progression-free survival in the ibrutinib-rituximab arm. Assays demonstrated enhanced anti-CLL T-cell killing function during ibrutinib-rituximab treatment, including a switch from predominantly CD4+ T-cell:CLL immune synapses at baseline to increased CD8+ lytic synapses on-therapy. Conversely, in the FCR arm, higher T-cell numbers correlated with adverse clinical responses and showed no functional improvement. We further demonstrate the potential of exploiting rejuvenated T-cell cytotoxicity during ibrutinib-rituximab treatment, using the bispecific antibody glofitamab, supporting combination immunotherapy approaches.","journal":"Blood","year":2023,"id":334834,"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":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9553,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":554639,"name":"Victoria Wang","orcid":"0000-0003-4079-5576","position":1,"is_corresponding":false},{"id":285630,"name":"Tait D. Shanafelt","orcid":"0000-0002-7106-5202","position":2,"is_corresponding":false},{"id":490131,"name":"Connie Lesnick","orcid":"0009-0008-2812-1214","position":3,"is_corresponding":false},{"id":1063752,"name":"Nikolaos Ioannou","orcid":"0000-0002-7956-5543","position":4,"is_corresponding":false},{"id":1063753,"name":"Giulia De Rossi","orcid":"0000-0001-6163-4590","position":5,"is_corresponding":false},{"id":52758,"name":"Sylvia Herter","orcid":"0000-0002-2446-696X","position":6,"is_corresponding":false},{"id":52759,"name":"Marina Bacac","orcid":"0000-0003-0581-9579","position":7,"is_corresponding":false},{"id":312004,"name":"Christian Klein","orcid":"0000-0001-7594-7280","position":8,"is_corresponding":false},{"id":108822,"name":"Martin S. Tallman","orcid":"0000-0002-4367-6102","position":9,"is_corresponding":false},{"id":451444,"name":"Neil E. Kay","orcid":"0000-0002-5951-5055","position":10,"is_corresponding":false},{"id":1063754,"name":"Alan G. Ramsay","orcid":"0000-0002-0452-0420","position":11,"is_corresponding":false},{"id":1063751,"name":"Despoina Papazoglou","orcid":"0009-0008-5818-8663","position":0,"is_corresponding":true}],"reference_count":25,"raw_metadata":null,"created_at":"2026-07-19T01:09:53.742667Z","pmid":"37824808","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":[]}