Management Principles Associated With Cytokine Release Syndrome

Baer, Brittney; Dudley, Channing V.; Simons, Rhea M.

doi:10.1016/j.soncn.2019.08.010

Cited by 8 publications

(3 citation statements)

References 7 publications

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“…toxicities The most commonly reported adverse event across all CAR T clinical trials is CRS, with rates ranging from 37% to 93% in patients with lymphoma treated with anti-CD19 CAR T cells and 77% to 93% in leukemia. [152][153][154][155][156][157] CRS has also been observed in patients with RRMM treated with BCMA-directed CAR T cells. 12 136-138 A consensus grading system for CRS has been developed by the American Society for Transplant and Cell Therapy (ASTCT), 158 and most clinical trials going forward in the MM setting are using the ASTCT criteria.…”

Section: Patient Selectionmentioning

confidence: 89%

“…Severe CRS may be fatal and requires intensive management, but most cases do resolve if care is initiated quickly, including IL-6 blockade and steroids. 153 156 157 159 The established protocol for IL-6 blockade involves tocilizumab, an antibody against the IL-6 receptor, initially developed for rheumatoid arthritis, which was approved in 2018 by the FDA for the treatment of CAR T cell-induced CRS. 160 161 Although some concerns have been raised that steroids or IL-6/IL-6R axis blockade may impair T-cell proliferation, several reports have described successful management of severe CAR T cell-associated CRS using IL-6R-directed therapy and short-course corticosteroids without apparent compromise in expansion or therapeutic efficacy.…”

Section: Car T Cellsmentioning

confidence: 99%

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The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of multiple myeloma

Shah

Aiello

Avigan

et al. 2020

J Immunother Cancer

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Outcomes in multiple myeloma (MM) have improved dramatically in the last two decades with the advent of novel therapies including immunomodulatory agents (IMiDs), proteasome inhibitors and monoclonal antibodies. In recent years, immunotherapy for the treatment of MM has advanced rapidly, with the approval of new targeted agents and monoclonal antibodies directed against myeloma cell-surface antigens, as well as maturing data from late stage trials of chimeric antigen receptor CAR T cells. Therapies that engage the immune system to treat myeloma offer significant clinical benefits with durable responses and manageable toxicity profiles, however, the appropriate use of these immunotherapy agents can present unique challenges for practicing physicians. Therefore, the Society for Immunotherapy of Cancer convened an expert panel, which met to consider the current role of approved and emerging immunotherapy agents in MM and provide guidance to the oncology community by developing consensus recommendations. As immunotherapy evolves as a therapeutic option for the treatment of MM, these guidelines will be updated.

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Section: Patient Selectionmentioning

confidence: 89%

Section: Car T Cellsmentioning

confidence: 99%

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of multiple myeloma

Shah

Aiello

Avigan

et al. 2020

J Immunother Cancer

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“…It is clinically presented with delirium, seizures, dizziness, decreased attention span, disorientation, ataxia, weakness, and sometimes headache as illustrated in Figure 2 . It may gradually progress to confusion, difficulty in speaking, and global aphasia after expressive aphasia in severe cases 16 , 40 , 41 . Neurotoxicity greater than grade 2 is severe and is presented with motor weakness, incontinence, mental obtundation, and increased intracranial pressure, which causes papilledema and cerebral edema 12 .…”

Section: Clinical Manifestations Of Car T-cell Associated Neurotoxicitymentioning

confidence: 99%

Toxicities of CAR T-cell therapy: a review of current literature

Asghar,

Ismail Shah,

Rani

et al. 2023

Annals of Medicine &Amp; Surgery

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The chimeric antigen receptor (CAR) design, first invented by Zelig Eshhar, paved the way for the use of genetically modified T-cells in targeted therapy against cancer cells. Since then, it has gone through many generations especially with the integration of co-stimulation in the second and third-generation CARs. However, it also mounts a hyperactive immune response named as cytokine release syndrome (CRS) with the release of several cytokines eventually resulting in multiple end-organ toxicities. The severity of CRS depends upon certain factors such as the tumor burden, choice of co-stimulation, and degree of lymphodepletion, and can manifest as pulmonary edema, vascular leak, renal dysfunction, cardiac problems, hepatic failure, and coagulopathy. Many grading criteria have been used to define these clinical manifestations but they lack harmonization. Neurotoxicity has also been significantly associated with CAR T-cell therapy but it has not been studied much in previous literature. This review aims to provide a comprehensive account of the clinical manifestations, diagnosis, management, and treatment of CAR T-cell associated neurotoxicity.

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