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Cited by 899

The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.

Recent advances in CAR T-cell toxicity: Mechanisms, manifestations and management

Open access
Brudno, Jennifer N., Kochenderfer, James N.·2019·Blood Reviews
DOI 10.1016/j.blre.2018.11.002
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Abstract

Chimeric antigen receptor (CAR) T-cell therapy is an effective new treatment for hematologic malignancies. Two CAR T-cell products are now approved for clinical use by the U.S. FDA: tisagenlecleucel for pediatric acute lymphoblastic leukemia (ALL) and adult diffuse large B-cell lymphoma subtypes (DLBCL), and axicabtagene ciloleucel for DLBCL. CAR T-cell therapies are being developed for multiple myeloma, and clear evidence of clinical activity has been generated. A barrier to widespread use of CAR T-cell therapy is toxicity, primarily cytokine release syndrome (CRS) and neurologic toxicity. Manifestations of CRS include fevers, hypotension, hypoxia, end organ dysfunction, cytopenias, coagulopathy, and hemophagocytic lymphohistiocytosis. Neurologic toxicities are diverse and include encephalopathy, cognitive defects, dysphasias, seizures, and cerebral edema. Our understanding of the pathophysiology of CRS and neurotoxicity is continually improving. Early and peak levels of certain cytokines, peak blood CAR T-cell levels, patient disease burden, conditioning chemotherapy, CAR T-cell dose, endothelial activation, and CAR design are all factors that may influence toxicity. Multiple grading systems for CAR T-cell toxicity are in use; a universal grading system is needed so that CAR T-cell products can be compared across studies. Guidelines for toxicity management vary among centers, but typically include supportive care, plus immunosuppression with tocilizumab or corticosteroids administered for severe toxicity. Gaining a better understanding of CAR T-cell toxicities and developing new therapies for these toxicities are active areas of laboratory research. Further clinical investigation of CAR T-cell toxicity is also needed. In this review, we present guidelines for management of CRS and CAR neurotoxicity.

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Metadata

Authors
Brudno, J. N., & Kochenderfer, J. N.
Venue
Blood Reviews
Publisher
Elsevier BV
Published
2019-03
Volume
34
Pages
45-55
ISSN
0268-960X (ISSN-L)
DOI
10.1016/j.blre.2018.11.002
OpenAlex
W2901262057
Cited by
899
References
19
FWCI
25.70
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Recent advances in CAR T-cell toxicity: Mechanisms, manifestations and management. https://app.cochat.ai/papers/10.1016/j.blre.2018.11.002
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Brudno, J. N., & Kochenderfer, J. N. (2019). Recent advances in CAR T-cell toxicity: Mechanisms, manifestations and management. Blood Reviews. https://doi.org/10.1016/j.blre.2018.11.002

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.