715 例患者观察性研究中 CAR-T 细胞疗效的昼夜节律

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.