Time of day of CAR T-cell infusion and outcomes in large B-cell lymphoma

Circadian rhythms orchestrate immune activation and effector function, yet whether within-day timing influences chimeric antigen receptor (CAR) T-cell therapy outcomes remains unknown. We conducted an international, multicenter retrospective study of 1052 adults with relapsed or refractory large B-cell lymphoma treated with CD19-directed CAR T-cell therapy across 7 centers (2017-2025). The median infusion time was 11:48 am (interquartile range, 11:06 am to 12:45 pm). Each hour later in infusion time was associated with an increased risk of progression, relapse, or death (hazard ratio, 1.11; 95% confidence interval, 1.03-1.20; P = .004) after adjustment for center, product, and key clinical variables. One-year progression-free survival (PFS) was 51.4% for early (before 12:00 noon) infusion vs 35.2% for late (at or after 12:00 noon) infusion, whereas overall survival was similar between groups. The PFS benefit was driven by lower relapse and higher complete response rates in the early infusion group. Although no differences were observed in immune toxicities, late infusion correlated with higher peak inflammatory markers and reduced day 7 CAR T-cell expansion. Together, these findings suggest that the timing of CAR T-cell infusion may influence therapeutic efficacy and support prospective evaluation of circadian-informed delivery strategies.

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Journal
Blood
Published
2026-01-05
DOI
https://doi.org/10.1182/blood.2025031476
Citations
1
Primary Topic
CAR-T cell therapy research
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article
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24.20
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Time of day of CAR T-cell infusion and outcomes in large B-cell lymphoma

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Time of day of CAR T-cell infusion and outcomes in large B-cell lymphoma

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article en
1 citations

Abstract

Circadian rhythms orchestrate immune activation and effector function, yet whether within-day timing influences chimeric antigen receptor (CAR) T-cell therapy outcomes remains unknown. We conducted an international, multicenter retrospective study of 1052 adults with relapsed or refractory large B-cell lymphoma treated with CD19-directed CAR T-cell therapy across 7 centers (2017-2025). The median infusion time was 11:48 am (interquartile range, 11:06 am to 12:45 pm). Each hour later in infusion time was associated with an increased risk of progression, relapse, or death (hazard ratio, 1.11; 95% confidence interval, 1.03-1.20; P = .004) after adjustment for center, product, and key clinical variables. One-year progression-free survival (PFS) was 51.4% for early (before 12:00 noon) infusion vs 35.2% for late (at or after 12:00 noon) infusion, whereas overall survival was similar between groups. The PFS benefit was driven by lower relapse and higher complete response rates in the early infusion group. Although no differences were observed in immune toxicities, late infusion correlated with higher peak inflammatory markers and reduced day 7 CAR T-cell expansion. Together, these findings suggest that the timing of CAR T-cell infusion may influence therapeutic efficacy and support prospective evaluation of circadian-informed delivery strategies.

BloodVol. 147(12)
Universidad Complutense de Madrid (ES), Universitat Autònoma de Barcelona (ES), Ben-Gurion University of the Negev (IL), Hackensack University Medical Center (US), Memorial Sloan Kettering Cancer Center (US), Tel Aviv University (IL), Technion – Israel Institute of Technology (IL), German Cancer Research Center (DE), Cornell University (US), Heidelberg University (DE), Tel Aviv Sourasky Medical Center (IL), Sheba Medical Center (IL), Soroka Medical Center (IL), Rambam Health Care Campus (IL), University Hospital Heidelberg (DE), LMU Klinikum (DE), Rappaport Family Institute for Research in the Medical Sciences (IL), Hackensack Meridian Health (US), Ludwig-Maximilians-Universität München (DE)
Good health and well-being
Openalex Percentile: Top 3%
CAR-T cell therapy research
24.20
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