Early Toxicities of CAR-T Cell Therapy: Mechanisms, Prediction, and Management
- 1School of Medicine, Wayne State University, Detroit, MI 48201, USA
- 2Hematology Oncology, Henry Ford Health, Detroit, MI 48236, USA
- 3Stem Cell Transplant and Cell Therapy, Henry Ford Health, Detroit, MI 48202, USA
Abstract
Chimeric antigen receptor T (CAR-T) cell therapy has completely reshaped the therapeutic landscape for some blood cancers, including B-cell lymphoma, myeloma, and acute lymphoblastic leukemia. However, the complications associated with this powerful therapy are preventing it from being used more widely. This review explores the underlying biology, clinical signs, and current treatments for the three major early CAR-T cell therapy-associated toxicities: cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome. Here, we outline key findings from preclinical animal models, data from multicenter clinical trials, and real-world patient cohort study data to delineate how infused cells and different host-derived and blood–brain barrier disruptions contribute to these adverse effects. A growing body of evidence is revealing that the patient’s own monocytes and macrophages, not just the infused CAR-T cells, may contribute to driving systemic toxicities primarily by releasing interleukin-1 (IL-1) and IL-6. A more thorough and mechanistically detailed understanding of CAR-T cell therapy-associated toxicity is needed to develop better predictive tools and treatment strategies so that patients derive the greatest antitumor benefits with the lowest risk of severe treatment-related complications.
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BibTeX
@article{srikantan2026early,
title = {{Early Toxicities of CAR-T Cell Therapy: Mechanisms, Prediction, and Management}},
author = {Swathi Srikantan and Alexander Weiss and Zainab Muslehuddin and Shatha Farhan},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219587},
url = {https://www.mdpi.com/1422-0067/27/21/9587},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Early Toxicities of CAR-T Cell Therapy: Mechanisms, Prediction, and Management
AU - Swathi Srikantan
AU - Alexander Weiss
AU - Zainab Muslehuddin
AU - Shatha Farhan
PY - 2026
DA - 2026/10/27
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219587
UR - https://www.mdpi.com/1422-0067/27/21/9587
AB - Chimeric antigen receptor T (CAR-T) cell therapy has completely reshaped the therapeutic landscape for some blood cancers, including B-cell lymphoma, myeloma, and acute lymphoblastic leukemia. However, the complications associated with this powerful therapy are preventing it from being used more widely. This review explores the underlying biology, clinical signs, and current treatments for the three major early CAR-T cell therapy-associated toxicities: cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome. Here, we outline key findings from preclinical animal models, data from multicenter clinical trials, and real-world patient cohort study data to delineate how infused cells and different host-derived and blood–brain barrier disruptions contribute to these adverse effects. A growing body of evidence is revealing that the patient’s own monocytes and macrophages, not just the infused CAR-T cells, may contribute to driving systemic toxicities primarily by releasing interleukin-1 (IL-1) and IL-6. A more thorough and mechanistically detailed understanding of CAR-T cell therapy-associated toxicity is needed to develop better predictive tools and treatment strategies so that patients derive the greatest antitumor benefits with the lowest risk of severe treatment-related complications.
SN - 1422-0067
ER -