{"doi":"10.1172/jci.insight.201159","title":"Diurnal rhythm in chimeric antigen receptor T cell effectiveness in an observational study of 715 patients","abstract":"BACKGROUNDChimeric antigen receptor (CAR) T cells are a leading immunotherapy for refractory B cell malignancies; however, their effect is limited by toxicity and incomplete efficacy. Daily (circadian) rhythms in immune function may offer a lever to boost therapeutic success; however, their clinical relevance to CAR T cell therapy remains unknown.METHODSWe retrospectively analyzed CAR T cell survival and complications based on infusion time at 2 geographically distinct hospitals: Washington University School of Medicine in St. Louis, Missouri, USA (n = 384) and Oregon Health & Science University in Portland, Oregon, USA (n = 331) between January 2018 and March 2025. The primary outcome was 90-day overall survival (OS). Secondary outcomes included event-free survival (EFS), cytokine release syndrome (CRS), immune cell-associated neurotoxicity syndrome (ICANS), ICU admission, shock, respiratory failure, and infection. We quantified the independent relationship between infusion time and outcomes using multivariable mixed-effects logistic regression and time-to-event models, adjusting for patient, oncologic, and treatment characteristics.RESULTSThe therapeutic index of CAR-T cells inversely correlated with the timing of administration, with later infusions associated with lower effectiveness and more adverse outcomes. For each hour that CAR T cell treatment was delayed, the adjusted odds ratio (aOR) of 90-day mortality increased by 24% (aOR 0.76; 95% CI 0.64-0.88, P = 0.001), severe neurotoxicity by 17% (P = 0.023), and mechanical ventilation by 27% (P = 0.026). These temporal patterns were most pronounced in patients receiving CD19-targeting CAR T cell products. In contrast, we did not find an association between infusion time and severe CRS (aOR 0.99; 95% CI, 0.75-1.27; P = 0.92).CONCLUSIONTime of day is a potent and easily modifiable factor that could optimize CAR T cell clinical performance.","journal":"JCI Insight","year":2025,"id":527862,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9401,"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":1405296,"name":"Eunsun Gill","orcid":"0000-0002-3504-2070","position":1,"is_corresponding":false},{"id":1405737,"name":"Prisha Kumar","orcid":null,"position":2,"is_corresponding":false},{"id":1405738,"name":"Melissa Beasley","orcid":null,"position":3,"is_corresponding":false},{"id":958994,"name":"Brenna Park-Egan","orcid":null,"position":4,"is_corresponding":false},{"id":732841,"name":"Zulfiqar A. Lokhandwala","orcid":"0000-0002-5000-4611","position":5,"is_corresponding":false},{"id":456346,"name":"Katie M. Lebold","orcid":"0000-0001-6913-3758","position":6,"is_corresponding":false},{"id":636672,"name":"Brandon Hayes‐Lattin","orcid":"0000-0002-4380-4573","position":7,"is_corresponding":false},{"id":302430,"name":"Catherine L. Hough","orcid":"0000-0001-6425-0867","position":8,"is_corresponding":false},{"id":1030766,"name":"Nathan Singh","orcid":"0000-0001-5174-0453","position":9,"is_corresponding":false},{"id":415793,"name":"Guy Hazan","orcid":"0000-0002-7372-6262","position":10,"is_corresponding":false},{"id":903885,"name":"Huram Mok","orcid":"0000-0003-0173-9918","position":11,"is_corresponding":false},{"id":684302,"name":"Janice M. Huss","orcid":null,"position":12,"is_corresponding":false},{"id":326208,"name":"Colleen McEvoy","orcid":"0009-0008-2566-191X","position":13,"is_corresponding":false},{"id":238440,"name":"Jeffrey A. Haspel","orcid":"0000-0001-5839-0265","position":14,"is_corresponding":false},{"id":420205,"name":"Patrick G. Lyons","orcid":"0000-0002-1557-2787","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T02:50:44.062153Z","pmid":"41411053","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":[]}