The incidence of cytokine release syndrome and neurotoxicity of CD19 chimeric antigen receptor–T cell therapy in the patient with acute lymphoblastic leukemia and lymphoma

Cao, Jinglin; Wang, Hui; Gao, Weijia; You, Jia; Wu, Lihua; Wang, Zheng-Xu

doi:10.1016/j.jcyt.2020.01.015

Cited by 33 publications

(24 citation statements)

References 50 publications

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“…Previous meta-analysis reported that the incidence of CRS in patients with hematological malignancies receiving CAR-T cell therapy is approximately 55.3% ( 16 ), and the incidence of severe cytokine release syndrome (sCRS) is approximately 18.5% ( 17 ). In addition, use of immune-targeted drugs such as Nivolumab ( 18 , 19 ) and Brentuximab Vedotin ( 20 ) is associated with severe CRS. In 2018, the American Society for Blood and Marrow Transplantation (ASBMT) stated that if after receiving any immunotherapy, the patient’s endogenous or induced immune effector cells are activated in large numbers, then symptoms for the resulting superphysiological response must include fever and may also include hypotension, capillary leakage (hypoxia), and end-organ dysfunction for the response to be referred as CRS ( 21 ).…”

Section: Adverse Reactions Related To Car-t Cell Therapymentioning

confidence: 99%

Reactions Related to CAR-T Cell Therapy

et al. 2021

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The application of chimeric antigen receptor (CAR) T-cell therapy as a tumor immunotherapy has received great interest in recent years. This therapeutic approach has been used to treat hematological malignancies solid tumors. However, it is associated with adverse reactions such as, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), off-target effects, anaphylaxis, infections associated with CAR-T-cell infusion (CTI), tumor lysis syndrome (TLS), B-cell dysplasia, hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS) and coagulation disorders. These adverse reactions can be life-threatening, and thus they should be identified early and treated effectively. In this paper, we review the adverse reactions associated with CAR-T cells, the mechanisms driving such adverse reactions, and strategies to subvert them. This review will provide important reference data to guide clinical application of CAR-T cell therapy.

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Section: Adverse Reactions Related To Car-t Cell Therapymentioning

confidence: 99%

Reactions Related to CAR-T Cell Therapy

et al. 2021

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“…Features of the CAR design are also likely to be relevant in predicting the incidence of toxicity [10,34,35]. In particular, the use of a humanised or murine single-chain variable fragment (scFv), the use of hinge and transmembrane domains derived from either the CD28 or the CD8α molecule, and the use of CD28 co-stimulatory moieties have all been postulated to be relevant to the likelihood of ICANS [35,36]. The currently licensed anti-CD19 CARs have scFvs derived from murine antibodies.…”

Section: Risk Factors For Icansmentioning

confidence: 99%

Neurological updates: neurological complications of CAR-T therapy

et al. 2020

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Chimeric antigen receptor (CAR)-expressing T cells now offer an effective treatment option for people with previously refractory B cell malignancies and are under development for a wide range of other tumours. However, neurological toxicity is a common complication of CAR-T cell therapy, seen in over 50% of recipients in some cohorts. Since 2018, the term immune effector cell-associated neurotoxicity syndrome (ICANS) has been used to describe and grade neurotoxicity seen after CAR-T cells and other similar therapies. ICANS following CAR-T therapy is usually self-limiting but can necessitate admission to the intensive care unit and is rarely fatal. As CAR-T therapies enter routine clinical practice, it is important for neurologists to be aware of the nature of neurological complications. Here, we summarise the clinical manifestations, mechanisms, investigations and recommended treatment of CAR-T-related neurotoxicity, focusing on the licensed CD19 products.

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“…Despite the remarkable clinical efficacy for patients with B-NHL or other B-cell malignancies, CAR-T cell-associated toxicities such as CRS can be observed in clinical trials, which limit the number of patients who are eligible for CAR-T cell therapy. CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) are the two most common CAR-T cell-associated toxicities [ 29 ].…”

Section: Discussion Of Clinical Trialsmentioning

confidence: 99%

Advances in chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma

2021

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B-cell non-Hodgkin lymphoma (B-NHL) is a group of heterogeneous disease which remains incurable despite developments of standard chemotherapy regimens and new therapeutic agents in decades. Some individuals could have promising response to standard therapy while others are unresponsive to standard chemotherapy or relapse after autologous hematopoietic stem-cell transplantation (ASCT), which indicates the necessity to develop novel therapies for refractory or relapsed B-NHLs. In recent years, a novel cell therapy, chimeric antigen receptor T-cell therapy (CAR-T), was invented to overcome the limitation of traditional treatments. Patients with aggressive B-NHL are considered for CAR-T cell therapy when they have progressive lymphoma after second-line chemotherapy, relapse after ASCT, or require a third-line therapy. Clinical trials of anti-CD19 CAR-T cell therapy have manifested encouraging efficacy in refractory or relapsed B-NHL. However, adverse effects of this cellular therapy including cytokine release syndrome, neurotoxicity, tumor lysis syndrome and on-target, off-tumor toxicities should attract our enough attention despite the great anti-tumor effects of CAR-T cell therapy. Although CAR-T cell therapy has shown remarkable results in patients with B-NHL, the outcomes of patients with B-NHL were inferior to patients with acute lymphoblastic leukemia. The inferior response rate may be associated with physical barrier of lymphoma, tumor microenvironment and low quality of CAR-T cells manufactured from B-NHL patients. Besides, some patients relapsed after anti-CD19 CAR-T cell therapy, which possibly were due to limited CAR-T cells persistence, CD19 antigen escape or antigen down-regulation. Quite a few new antigen-targeted CAR-T products and new-generation CAR-T, for example, CD20-targeted CAR-T, CD79b-targeted CAR-T, CD37-targeted CAR-T, multi-antigen-targeted CAR-T, armored CAR-T and four-generation CAR-T are developing rapidly to figure out these deficiencies.

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The incidence of cytokine release syndrome and neurotoxicity of CD19 chimeric antigen receptor–T cell therapy in the patient with acute lymphoblastic leukemia and lymphoma

Cited by 33 publications

References 50 publications

Reactions Related to CAR-T Cell Therapy

Reactions Related to CAR-T Cell Therapy

Neurological updates: neurological complications of CAR-T therapy

Advances in chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma

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