Time of day of CAR T-cell infusion and outcomes in large B-cell lymphoma
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.
Article Details
Authors (43)
Danny Luan
1Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
Ori Ben Valid
3Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel HaShomer, Ramat Gan, Israel
Ofrat Beyar-Katz
5Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel
Tobias Tix
7Department of Medicine III, Hematology/Oncology, LMU University Hospital, LMU Munich, Munich, Germany
Noa Golan Accav
3Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel HaShomer, Ramat Gan, Israel
Mohammad Alhomoud
1Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
Abraham Avigdor
3Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel HaShomer, Ramat Gan, Israel
Veit L. Bücklein
7Department of Medicine III, Hematology/Oncology, LMU University Hospital, LMU Munich, Munich, Germany
Limor Cohen
Parastoo B. Dahi
1Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
Sigrun Einarsdottir
1Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
Julia Elimelech
5Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel
Silvia Escribano-Serrat
1Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
Lorenzo Falchi
Memorial Sloan Kettering Cancer Center, New York
Teng Fei
College of Life and Health Sciences, Northeastern University
Sergio Giralt
1Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
Marina Gomez-Llobell
1Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
Andre Goy
14Division of Oncology, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack Meridian Health, Hackensack, NJ
Nurit Horesh
Sapir Israeli
1Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
Linus Kruk
7Department of Medicine III, Hematology/Oncology, LMU University Hospital, LMU Munich, Munich, Germany
Lori Leslie
14Division of Oncology, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack Meridian Health, Hackensack, NJ
Jennifer K. Lue
2Department of Medicine, Weill Cornell Medical College, New York, NY
Ronit Marcus
3Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel HaShomer, Ramat Gan, Israel
Arnon Nagler
3Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel HaShomer, Ramat Gan, Israel
M. Lia Palomba
5Memorial Sloan Kettering Cancer Center, New York, NY
Jae H. Park
Sandeep Raj
1Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
Siddhartha Reddy
14Division of Oncology, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack Meridian Health, Hackensack, NJ
Jason Romancik
14Division of Oncology, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack Meridian Health, Hackensack, NJ
Efrat Rosenbaum
15Hematology Division, Bone Marrow Transplant Unit, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel
Gilles Salles
41Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY
Michael Scordo
Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York
Gunjan L. Shah
Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York
Avichai Shimoni
3Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel HaShomer, Ramat Gan, Israel
Michael von Bergwelt-Baildon
Ludwig Maximilian University Hospital, Munich, Germany
Miguel-Angel Perales
1Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY
Marion Subklewe
Ludwig Maximilian University Hospital, Munich, Germany
Uri Greenbaum
8Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
Andrew Ip
14Division of Oncology, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack Meridian Health, Hackensack, NJ
Ron Ram
15Hematology Division, Bone Marrow Transplant Unit, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel
Kai Rejeski
Memorial Sloan Kettering Cancer Center, New York, New York, United States
Roni Shouval
1Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY