Overview of Adverse Events Associated with Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy
Ekaterina Vorozheikina, Magdalena Ruiz, Leticia Solari, Dmitry Ostasevich, Luis Mendoza
International Blood Research & Reviews · pp. 11–31 · Published 2 Sep 2021
10.9734/ibrr/2021/v12i430157Abstract
Anti-CD19 chimeric antigen receptor (CAR) T-cells represent a novel immunotherapy that has shown remarkable success in the treatment of adult relapsed or refractory (R/R) B-cell non-Hodgkin's lymphoma, adult R/R mantle cell lymphoma, and R/R acute paediatric lymphoblastic leukaemia. One barrier to the widespread use of CAR T-cell therapy is toxicity, primarily cytokine release syndrome (CRS) with a variable grade of severity. The main manifestations of CRS are fever, hypotension, cytopenia, organ dysfunction among others. Neurological toxicities vary widely and range from headaches to encephalopathy. In addition, anti-CD19 CAR T-cell therapy provokes an array of less frequent events, such as coagulopathies, delayed cytopenia, and cardiovascular toxicities. In general, toxicities are usually reversible and resolve on their own in most cases, though severe cases may require intensive care and immunosuppressive therapy. Deaths due to CRS, neurologic toxicity and infectious complications have been reported, which highlights the gravity of these syndromes and the critical nature of appropriate intervention. In this paper, we look at all available FDA- and EMA-approved information about the pathophysiology, clinical manifestations, risk factor reviews of existing toxicity grading systems, current management strategies, and guidelines for anti-CD19 CAR T-cell toxicities. We also present new approaches, which are under investigation, to mitigate these adverse events.
References (66)
- 1 Correspondence - Tranexamic acid for traumatic brain injury [DOI]
- 2 Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma [DOI]
- 3 Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia [DOI]
- 4 Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia [DOI]
- 5 Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma [DOI]
- 6 Chimeric Antigen Receptor–Modified T Cells for Acute Lymphoid Leukemia [DOI]
- 7 The pro- and anti-inflammatory properties of the cytokine interleukin-6 [DOI]
- 8 T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial [DOI]
- 9 Current concepts in the diagnosis and management of cytokine release syndrome [DOI]
- 10 Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia [DOI]
- 11 IL-6 as a keystone cytokine in health and disease [DOI]
- 12 Efficacy and Toxicity Management of 19-28z CAR T Cell Therapy in B Cell Acute Lymphoblastic Leukemia [DOI]
- 13 Chimeric antigen receptor T-cell therapy — assessment and management of toxicities [DOI]
- 14 Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1–2 trial [DOI]
- 15 CD19 CAR–T cells of defined CD4+:CD8+ composition in adult B cell ALL patients [DOI]
- 16 CD19-Targeted T Cells Rapidly Induce Molecular Remissions in Adults with Chemotherapy-Refractory Acute Lymphoblastic Leukemia [DOI]
- 17 Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors. [DOI]
- 18 Cytokine release syndrome [DOI]
- 19 The Basic Principles of Chimeric Antigen Receptor Design [DOI]
- 20 Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR T cells [DOI]
- 21 Endothelial Activation and Blood–Brain Barrier Disruption in Neurotoxicity after Adoptive Immunotherapy with CD19 CAR-T Cells [DOI]
- 22 CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy [DOI]
- 23 Isolation of cDNA clones encoding T cell-specific membrane-associated proteins [DOI]
- 24 Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor–modified T-cell therapy [DOI]
- 25 Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults [DOI]
- 26 Identification of Predictive Biomarkers for Cytokine Release Syndrome after Chimeric Antigen Receptor T-cell Therapy for Acute Lymphoblastic Leukemia [DOI]
- 27 Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8 + T cells [DOI]
- 28 Clinical and Biological Correlates of Neurotoxicity Associated with CAR T-cell Therapy in Patients with B-cell Acute Lymphoblastic Leukemia [DOI]
- 29 Recent advances in CAR T-cell toxicity: Mechanisms, manifestations and management [DOI]
- 30 Immunotherapeutic Implications of Il-6 Blockade for Cytokine Storm [DOI]
- 31 Durable Molecular Remissions in Chronic Lymphocytic Leukemia Treated With CD19-Specific Chimeric Antigen Receptor–Modified T Cells After Failure of Ibrutinib [DOI]
- 32 Chimeric Antigen Receptor T Cells against CD19 for Multiple Myeloma [DOI]
- 33 Phase 1 Results of ZUMA-1: A Multicenter Study of KTE-C19 Anti-CD19 CAR T Cell Therapy in Refractory Aggressive Lymphoma [DOI]
- 34 Targeting tumours with genetically enhanced T lymphocytes [DOI]
- 35 Swelling of the optic nerve head: a staging scheme [DOI]
- 36 Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy [DOI]
- 37 Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors [DOI]
- 38 Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel [DOI]
- 39 Adoptive transfer of syngeneic T cells transduced with a chimeric antigen receptor that recognizes murine CD19 can eradicate lymphoma and normal B cells [DOI]
- 40 Chimeric Antigen Receptor T Cell–Mediated Neurotoxicity in Nonhuman Primates [DOI]
- 41 Effective response and delayed toxicities of refractory advanced diffuse large B-cell lymphoma treated by CD20-directed chimeric antigen receptor-modified T cells [DOI]
- 42 Measuring IL-6 and sIL-6R in serum from patients treated with tocilizumab and/or siltuximab following CAR T cell therapy [DOI]
- 43 Cytokine release syndrome and neurotoxicity after CD 19 chimeric antigen receptor‐modified ( CAR ‐) T cell therapy [DOI]
- 44 Monocyte lineage–derived IL-6 does not affect chimeric antigen receptor T-cell function [DOI]
- 45 Modification of the anti‐CD3‐induced cytokine release syndrome by anti‐interferon‐γ or anti‐interleukin‐6 antibody treatment: Protective effects and biphasic changes in blood cytokine levels [DOI]
- 46 The severe cytokine release syndrome in phase I trials of CD19-CAR-T cell therapy: a systematic review [DOI]
- 47 Updated safety and long term clinical outcomes in TRANSCEND NHL 001, pivotal trial of lisocabtagene maraleucel (JCAR017) in R/R aggressive NHL. [DOI]
- 48 Axicabtagene Ciloleucel (Axi-cel) CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy for Relapsed/Refractory Large B-Cell Lymphoma: Real World Experience [DOI]
- 49 Baseline and early post-treatment clinical and laboratory factors associated with severe neurotoxicity following 19-28z CAR T cells in adult patients with relapsed B-ALL. [DOI]
- 50 Impact of disease burden on long-term outcome of 19-28z CAR modified T cells in adult patients with relapsed B-ALL. [DOI]
- 51 ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells [DOI]
- 52 KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma [DOI]
- 53 Recommendations for the management of hemophagocytic lymphohistiocytosis in adults [DOI]
- 54 The tyrosine kinase inhibitor dasatinib acts as a pharmacologic on/off switch for CAR T cells [DOI]
- 55 IL-6 trans-signaling induces plasminogen activator inhibitor-1 from vascular endothelial cells in cytokine release syndrome [DOI]
- 56 Managing the toxicities of CAR T‐cell therapy [DOI]
- 57 Infection during the first year in patients treated with CD19 CAR T cells for diffuse large B cell lymphoma [DOI]
- 58 CAR T‐cell therapy: Full speed ahead [DOI]
- 59 DLBCL patients treated with CD19 CAR T cells experience a high burden of organ toxicities but low nonrelapse mortality [DOI]
- 60 In the Eye of the Storm: Immune‐mediated Toxicities Associated With CAR‐T Cell Therapy [DOI]
- 61 Spotlight on Tocilizumab in the Treatment of CAR-T-Cell-Induced Cytokine Release Syndrome: Clinical Evidence to Date. [DOI]
- 62 Coagulation Disorders after Chimeric Antigen Receptor T Cell Therapy: Analysis of 100 Patients with Relapsed and Refractory Hematologic Malignancies [DOI]
- 63 Venous thromboembolism associated with CD19-directed CAR T-cell therapy in large B-cell lymphoma [DOI]
- 64 IFN-γ and TNF-α aggravate endothelial damage caused by CD123-targeted CAR T cell [DOI]
- 65 Cardiovascular Complications of Chimeric Antigen Receptor T-Cell Therapy: The Cytokine Release Syndrome and Associated Arrhythmias [DOI]
- 66 Sustained Disease Control for Adult Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma: An Updated Analysis of Juliet, a Global Pivotal Phase 2 Trial of Tisagenlecleucel [DOI]
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