Neurotoxicity and Cytokine Release Syndrome After Chimeric Antigen Receptor T Cell Therapy: Insights Into Mechanisms and Novel Therapies

Trial in Progress: A Phase 2, Single-Arm, Open-Label Study of Itacitinib (ITA) for the Prevention of Chimeric Antigen Receptor (CAR) T-Cell–Induced Cytokine Release Syndrome (CRS)

(2020) Jae H. Park et al.   BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION

Pivotal Safety and Efficacy Results from Transcend NHL 001, a Multicenter Phase 1 Study of Lisocabtagene Maraleucel (liso-cel) in Relapsed/Refractory (R/R) Large B Cell Lymphomas

(2020) Jeremy S. Abramson et al.   BLOOD

Feasibility and efficacy of CD19-targeted CAR-T cells with concurrent ibrutinib for CLL after ibrutinib failure

(2020) Jordan Gauthier et al.   BLOOD

Immune Checkpoint Inhibitor-Related Cytokine Release Syndrome: Analysis of WHO Global Pharmacovigilance Database

(2020) Alessandro Ceschi et al.   Frontiers in Pharmacology

Mechanisms of resistance to CAR T cell therapy

(2019) Nirali N. Shah et al.   Nature Reviews Clinical Oncology

Pilot Trial of Adoptive Transfer of Chimeric Antigen Receptor–transduced T Cells Targeting EGFRvIII in Patients With Glioblastoma

(2019) Stephanie L. Goff et al.   JOURNAL OF IMMUNOTHERAPY

Granulocyte-macrophage colony-stimulating factor inactivation in CAR T-Cells prevents monocyte-dependent release of key cytokine release syndrome mediators

(2019) Mohit Sachdeva et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Toxicities of CD19 CAR-T cell immunotherapy

(2019) Alexandre V. Hirayama et al.   AMERICAN JOURNAL OF HEMATOLOGY

Managing the toxicities of CAR T‐cell therapy

(2019) Sattva S. Neelapu   HEMATOLOGICAL ONCOLOGY

The tyrosine kinase inhibitor dasatinib acts as a pharmacologic on/off switch for CAR T cells

(2019) Katrin Mestermann et al.   Science Translational Medicine

Comparative Review of 30 Day Non-Relapse Mortality (NRM) in B-Cell Lymphomas Associated with Anti-CD19 Chimeric Antigen Receptor T-Cells (CAR-T) from FDA Database, Clinical Studies, and MD Anderson

(2019) Ethan Burns et al.   BLOOD

Prophylactic Itacitinib (INCB039110) for the Prevention of Cytokine Release Syndrome Induced By Chimeric Antigen Receptor T-Cells (CAR-T-cells) Therapy

(2019) Eduardo Huarte et al.   BLOOD

Mechanisms of Relapse After CD19 CAR T-Cell Therapy for Acute Lymphoblastic Leukemia and Its Prevention and Treatment Strategies

(2019) Xinjie Xu et al.   Frontiers in Immunology

Mechanisms Underlying the Anti-inflammatory and Immunosuppressive Activity of Ruxolitinib

(2019) Elena Maria Elli et al.   Frontiers in Oncology

Preemptive mitigation of CD19 CAR T-cell cytokine release syndrome without attenuation of antileukemic efficacy

(2019) Rebecca A. Gardner et al.   BLOOD

Incorporation of Immune Checkpoint Blockade into Chimeric Antigen Receptor T Cells (CAR-Ts): Combination or Built-In CAR-T

(2018) Dok Yoon et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

T Cells Genetically Modified to Express an Anti–B-Cell Maturation Antigen Chimeric Antigen Receptor Cause Remissions of Poor-Prognosis Relapsed Multiple Myeloma

(2018) Jennifer N. Brudno et al.   JOURNAL OF CLINICAL ONCOLOGY

Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR T cells

(2018) Margherita Norelli et al.   NATURE MEDICINE

CAR T cell–induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade

(2018) Theodoros Giavridis et al.   NATURE MEDICINE

Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia

(2018) Shannon L. Maude et al.   NEW ENGLAND JOURNAL OF MEDICINE

Clinical and Biologic Correlates of Neurotoxicity Associated with CAR T Cell Therapy in Patients with B-cell Acute Lymphoblastic Leukemia (B-ALL)

(2018) Bianca D. Santomasso et al.   Cancer Discovery

Chimeric Antigen Receptor T Cell–Mediated Neurotoxicity in Nonhuman Primates

(2018) Agne Taraseviciute et al.   Cancer Discovery

ASBMT Pharmacy Special Interest Group Survey on CAR T Cell Therapy Administrative, Logistical and Toxicity Management Practices in the United States

(2018) Zahra Mahmoudjafari et al.   BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION

Neuropathology of a Case With Fatal CAR T-Cell-Associated Cerebral Edema

(2018) Matthew Torre et al.   JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY

Management guidelines for paediatric patients receiving chimeric antigen receptor T cell therapy

(2018) Kris M. Mahadeo et al.   Nature Reviews Clinical Oncology

ASBMT Consensus Grading for Cytokine Release Syndrome and Neurological Toxicity Associated with Immune Effector Cells

(2018) Daniel W Lee et al.   BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION

GM-CSF inhibition reduces cytokine release syndrome and neuroinflammation but enhances CAR-T cell function in xenografts

(2018) Rosalie M. Sterner et al.   BLOOD

Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma

(2018) Stephen J. Schuster et al.   NEW ENGLAND JOURNAL OF MEDICINE

A Personalized Diagnostic and Treatment Approach for Macrophage Activation Syndrome and Secondary Hemophagocytic Lymphohistiocytosis in Adults

(2017) Bharat Kumar et al.   JOURNAL OF CLINICAL IMMUNOLOGY

Inducible Caspase-9 Selectively Modulates the Toxicities of CD19-Specific Chimeric Antigen Receptor-Modified T Cells

(2017) Iulia Diaconu et al.   MOLECULAR THERAPY

CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy

(2017) Terry J Fry et al.   NATURE MEDICINE

Chimeric antigen receptor T-cell therapy — assessment and management of toxicities

(2017) Sattva S. Neelapu et al.   Nature Reviews Clinical Oncology

Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas

(2017) Stephen J. Schuster et al.   NEW ENGLAND JOURNAL OF MEDICINE

Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma

(2017) Sattva S. Neelapu et al.   NEW ENGLAND JOURNAL OF MEDICINE

A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma

(2017) Donald M. O’Rourke et al.   Science Translational Medicine

Endothelial Activation and Blood–Brain Barrier Disruption in Neurotoxicity after Adoptive Immunotherapy with CD19 CAR-T Cells

(2017) Juliane Gust et al.   Cancer Discovery

Phase I study of chimeric antigen receptor modified T cells in treating HER2-positive advanced biliary tract cancers and pancreatic cancers

(2017) Kaichao Feng et al.   Protein & Cell

Interleukin 1 Receptor Antagonist Anakinra, Intravenous Immunoglobulin, and Corticosteroids in the Management of Critically Ill Adult Patients With Hemophagocytic Lymphohistiocytosis

(2017) Philipp Wohlfarth et al.   JOURNAL OF INTENSIVE CARE MEDICINE

Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer

(2017) Kristen M. Hege et al.   Journal for ImmunoTherapy of Cancer

Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure

(2016) P. G. Richardson et al.   BLOOD

Toxicities of chimeric antigen receptor T cells: recognition and management

(2016) Jennifer N. Brudno et al.   BLOOD

Ibrutinib enhances chimeric antigen receptor T-cell engraftment and efficacy in leukemia

(2016) Joseph A. Fraietta et al.   BLOOD

The Addition of the BTK Inhibitor Ibrutinib to Anti-CD19 Chimeric Antigen Receptor T Cells (CART19) Improves Responses against Mantle Cell Lymphoma

(2016) M. Ruella et al.   CLINICAL CANCER RESEARCH

Distinct Signaling of Coreceptors Regulates Specific Metabolism Pathways and Impacts Memory Development in CAR T Cells

(2016) Omkar U. Kawalekar et al.   IMMUNITY

CD19 CAR–T cells of defined CD4+:CD8+ composition in adult B cell ALL patients

(2016) Cameron J. Turtle et al.   JOURNAL OF CLINICAL INVESTIGATION

Kinase inhibitor ibrutinib to prevent cytokine-release syndrome after anti-CD19 chimeric antigen receptor T cells for B-cell neoplasms

(2016) M Ruella et al.   LEUKEMIA

Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy

(2016) Christine E. Brown et al.   NEW ENGLAND JOURNAL OF MEDICINE

Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer

(2016) Kaichao Feng et al.   Science China-Life Sciences

Identification of Predictive Biomarkers for Cytokine Release Syndrome after Chimeric Antigen Receptor T-cell Therapy for Acute Lymphoblastic Leukemia

(2016) D. T. Teachey et al.   Cancer Discovery

CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia

(2015) S. L. Maude et al.   BLOOD

Structural Design of Engineered Costimulation Determines Tumor Rejection Kinetics and Persistence of CAR T Cells

(2015) Zeguo Zhao et al.   CANCER CELL

Bioactivity and Safety of IL13R 2-Redirected Chimeric Antigen Receptor CD8+ T Cells in Patients with Recurrent Glioblastoma

(2015) C. E. Brown et al.   CLINICAL CANCER RESEARCH

T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial

(2015) Daniel W Lee et al.   LANCET

Convergence of Acquired Mutations and Alternative Splicing of CD19 Enables Resistance to CART-19 Immunotherapy

(2015) E. Sotillo et al.   Cancer Discovery

Managing Cytokine Release Syndrome Associated With Novel T Cell-Engaging Therapies

(2014) Shannon L. Maude et al.   CANCER JOURNAL

Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia

(2014) Shannon L. Maude et al.   NEW ENGLAND JOURNAL OF MEDICINE

Therapeutic Role of Anakinra, an Interleukin-1 Receptor Antagonist, in the Management of Secondary Hemophagocytic Lymphohistiocytosis/Sepsis/Multiple Organ Dysfunction/Macrophage Activating Syndrome in Critically Ill Children*

(2014) Surender Rajasekaran et al.   Pediatric Critical Care Medicine

Efficacy and Toxicity Management of 19-28z CAR T Cell Therapy in B Cell Acute Lymphoblastic Leukemia

(2014) M. L. Davila et al.   Science Translational Medicine

Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes

(2013) J. A. Dubovsky et al.   BLOOD

Chimeric Antigen Receptor–Modified T Cells for Acute Lymphoid Leukemia

(2013) Stephan A. Grupp et al.   NEW ENGLAND JOURNAL OF MEDICINE

Combining a CD20 Chimeric Antigen Receptor and an Inducible Caspase 9 Suicide Switch to Improve the Efficacy and Safety of T Cell Adoptive Immunotherapy for Lymphoma

(2013) Lihua E. Budde et al.   PLoS One

B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells

(2011) J. N. Kochenderfer et al.   BLOOD

A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells

(2011) X. Wang et al.   BLOOD

Chimeric Antigen Receptor–Modified T Cells in Chronic Lymphoid Leukemia

(2011) David L. Porter et al.   NEW ENGLAND JOURNAL OF MEDICINE

T Cells with Chimeric Antigen Receptors Have Potent Antitumor Effects and Can Establish Memory in Patients with Advanced Leukemia

(2011) M. Kalos et al.   Science Translational Medicine

Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety

(2010) V Hoyos et al.   LEUKEMIA

Case Report of a Serious Adverse Event Following the Administration of T Cells Transduced With a Chimeric Antigen Receptor Recognizing ERBB2

(2010) Richard A Morgan et al.   MOLECULAR THERAPY