Year: 2026
Type: article
Study design: Observational Study
Abstract: 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.
Source: Blood
Authors: Danny Luan, Ori Ben Valid, Ofrat Beyar-Katz, Tobias Tix, Noa Golan Accav, Mohammad Alhomoud, Abraham Avigdor, Veit L. Bücklein, Limor Cohen, Parastoo B. Dahi, Sigrun Einarsdottir, Julia Elimelech, Silvia Escribano-Serrat, Lorenzo Falchi, Teng Fei, Sergio Giralt, Marina Gomez-Llobell, Andre Goy, Nurit Horesh, Sapir Israeli, Linus Kruk, Lori Leslie, Jennifer K. Lue, Ronit Marcus, Arnon Nagler, M. Lia Palomba, Jae H. Park, Sandeep Raj, Siddhartha Reddy, Jason Romancik, Efrat Rosenbaum, Gilles Salles, Michael Scordo, Gunjan L. Shah, Avichai Shimoni, Michael von Bergwelt-Baildon, Miguel-Angel Perales, Marion Subklewe, Uri Greenbaum, Andrew Ip, Ron Ram, Kai Rejeski, Roni Shouval
Institutions: Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, Tel Aviv University, Sheba Medical Center, Technion – Israel Institute of Technology, Rambam Health Care Campus, LMU Klinikum, Ludwig-Maximilians-Universität München, Ben-Gurion University of the Negev, Universitat Autònoma de Barcelona, Universidad Complutense de Madrid, Hackensack University Medical Center, Hackensack Meridian Health, Tel Aviv Sourasky Medical Center, German Cancer Research Center, Soroka Medical Center
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7118177011