A Primer on Chimeric Antigen Receptor T-cell Therapy-related Toxicities for the Intensivist

Review Oncology

Dose fractionation of CAR-T cells. A systematic review of clinical outcomes

Matthew Frigault et al.

Summary: CAR-T cells have the potential to successfully treat hematologic cancers, but severe adverse events are a concern. This study aims to assess whether dividing the dose of CAR-T cells reduces toxicity without affecting efficacy.

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH (2023)

添加到收藏夹

Letter Hematology

Interferon-γ blockade in CAR T-cell therapy-associated macrophage activation syndrome/hemophagocytic lymphohistiocytosis

Michael Rainone et al.

BLOOD ADVANCES (2023)

添加到收藏夹

Article Clinical Neurology

Continuous EEG monitoring detects nonconvulsive seizure and Ictal-Interictal Continuum abnormalities in moderate to severe ICANS following systemic CAR-T therapy

Sammita Satyanarayan et al.

Summary: In this study, the incidence of seizures and EEG abnormalities in patients with ICANS receiving axi-cel therapy was characterized. The results showed that 7.1% of the total cohort and 12% of patients with ICANS experienced seizures. Ictal-interictal continuum abnormalities, especially generalized periodic discharges, were also frequently observed in ICANS patients.

NEUROHOSPITALIST (2023)

添加到收藏夹

Article Hematology

Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome

Melissa R. Hines et al.

TRANSPLANTATION AND CELLULAR THERAPY (2023)

添加到收藏夹

Review Allergy

Hypogammaglobulinemia After Chimeric Antigen Receptor (CAR) T-Cell Therapy: Characteristics, Management, and Future Directions

Jeanette Wat et al.

Summary: Chimeric antigen receptor (CAR) T-cell therapy is a dynamic treatment for hematologic malignancies that offers long-term remissions but can have life-threatening side effects, including severe infections. B-cell aplasia is a common side effect that leads to hypogammaglobulinemia. This review discusses the occurrence, duration, and immune recovery of hypogammaglobulinemia observed in approved CAR T-cell therapies and clinical trials. It also explores the association between hypogammaglobulinemia and infections, with a focus on management strategies for evaluation and immunoglobulin replacement. The review also highlights newer CAR T-cell products targeting different B-cell antigens and identifies areas for future study to address hypogammaglobulinemia resulting from this therapy.

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE (2022)

添加到收藏夹

Article Oncology

Single-center experience using anakinra for steroid-refractory immune effector cell-associated neurotoxicity syndrome (ICANS)

Marc Wehrli et al.

Summary: Chimeric antigen receptor (CAR) T-cell therapy, while effective in treating tumors, is associated with acute toxicities including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Current treatment guidelines for CRS and ICANS recommend the use of tocilizumab and corticosteroids. This study retrospectively analyzed the use of anakinra, a drug that blocks the interleukin-1 receptor, in managing steroid-refractory ICANS. The use of anakinra resulted in significant reduction in fever and inflammatory cytokines, but did not have a dramatic effect on neurotoxicity or the tapering of corticosteroids.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2022)

添加到收藏夹

Article Critical Care Medicine

Critically Ill Patients Treated for Chimeric Antigen Receptor-Related Toxicity: A Multicenter Study*

Cristina Gutierrez et al.

Summary: This retrospective cohort study reports the epidemiology, treatments, and outcomes of adult patients admitted to the ICU after experiencing cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome following chimeric antigen receptor T-cell therapy. Despite the severity of toxicities, the need for organ support and ICU mortality were low in this patient population.

CRITICAL CARE MEDICINE (2022)

添加到收藏夹

Article Oncology

The CAR-HEMATOTOX risk-stratifies patients for severe infections and disease progression after CD19 CAR-T in R/R LBCL

Kai Rejeski et al.

Summary: The study demonstrates the utility of the HT score for risk-stratifying patients for infectious complications and poor survival outcomes prior to CD19 CAR-T therapy. High-risk patients may benefit from anti-infective prophylaxis and close monitoring for potential infections and relapse. Patients with high HT scores are more likely to develop severe infections, which represent a common cause of non-relapse mortality after CAR-T.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2022)

添加到收藏夹

Letter Hematology

Anakinra utilization in refractory pediatric CAR T-cell associated toxicities

Caroline Diorio et al.

BLOOD ADVANCES (2022)

添加到收藏夹

Review Oncology

Dose-response correlation for CAR-T cells: a systematic review of clinical studies

Anand Rotte et al.

Summary: The dose-dependent effects of CAR-T cell therapy on response and toxicity in hematological cancers were investigated. It was found that there is an optimal dose at which the clinical efficacy is highest, and further dose escalation may not improve response rates but can increase the incidence and severity of adverse events.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2022)

添加到收藏夹

Article Clinical Neurology

Long-term Neurologic Safety in Patients With B-Cell Lymphoma Treated With Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy

Renata Ursu et al.

Summary: No significant neurocognitive or neurologic disorders were observed in patients 2 years after treatment with anti-CD19 CAR T cells. Anxiety scores were reduced, but 32% of patients still reported cognitive complaints.

NEUROLOGY (2022)

添加到收藏夹

Article Critical Care Medicine

The use of ICU resources in CAR-T cell recipients: a hospital-wide study

Sandrine Valade et al.

Summary: CAR-T cell therapy is effective for refractory hematological malignancies, and intensive care management is crucial for CAR-T cell recipients. This retrospective study analyzed critically ill CAR-T cell recipients and found that complications such as cytokine release syndrome and bacterial infection were common. The severity of organ dysfunction was a major determinant of mortality.

ANNALS OF INTENSIVE CARE (2022)

添加到收藏夹

Meeting Abstract Hematology

Siltuximab for First-Line Treatment of Cytokine Release Syndrome: A Response to the National Shortage of Tocilizumab

Seema Patel et al.

BLOOD (2022)

添加到收藏夹

Meeting Abstract Hematology

The CAR-Hematotox Score As a Prognostic Model of Toxicity and Response in Patients Receiving BCMA-Directed CAR-T for Relapsed/Refractory Multiple Myeloma

Kai Rejeski et al.

BLOOD (2022)

添加到收藏夹

Meeting Abstract Hematology

The CAR-Hematotox Score Identifies Patients at High Risk for Hematological Toxicity, Infections and Poor Clinical Outcomes Following Brexucabtagene Autoleucel in Relapsed/Refractory Mantle Cell Lymphoma

Kai Rejeski et al.

BLOOD (2022)

添加到收藏夹

Review Immunology

Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy

Emma C. Morris et al.

Summary: CAR T cell therapy has revolutionized the field of cancer treatment, but significant toxicities can occur in up to one-third of patients. The most common toxicities include cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. Understanding their pathophysiology is crucial for developing novel therapeutics for prevention and management.

NATURE REVIEWS IMMUNOLOGY (2022)

添加到收藏夹

Review Medicine, Research & Experimental

Toward Better Understanding and Management of CAR-T Cell-Associated Toxicity

Andrea Schmidts et al.

Summary: CAR-T cell therapy has revolutionized the treatment of hematological malignancies, particularly acute lymphoblastic leukemia and large B cell lymphoma. However, it is associated with toxicities such as cytokine release syndrome and ICANS, which require further research and attention to manage effectively.

ANNUAL REVIEW OF MEDICINE, VOL 72, 2021 (2021)

添加到收藏夹

Meeting Abstract Hematology

A Phase II Study of Prophylactic Anakinra to Prevent CRS and Neurotoxicity in Patients Receiving CD19 CAR T Cell Therapy for Relapsed or Refractory Lymphoma

Jae H. Park et al.

BLOOD (2021)

添加到收藏夹

Article Hematology

Earlier corticosteroid use for adverse event management in patients receiving axicabtagene ciloleucel for large B-cell lymphoma

Max S. Topp et al.

Summary: The study assessed the impact of early corticosteroid and tocilizumab use on cytokine release syndrome and neurologic events in patients with refractory large B-cell lymphoma receiving axi-cel therapy. Results indicate that early and planned use of these drugs may decrease the incidence of severe cytokine release syndrome and neurologic events.

BRITISH JOURNAL OF HAEMATOLOGY (2021)

添加到收藏夹

Article Cell Biology

Ruxolitinib mitigates steroid-refractory CRS during CAR T therapy

Jing Pan et al.

Summary: The study evaluated the efficacy of the oral JAK inhibitor Ruxolitinib in treating cytokine release syndrome (CRS) associated with leukemia treatment. The findings suggest that Ruxolitinib is active and well tolerated in patients with steroid-refractory or life-threatening CRS.

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE (2021)

添加到收藏夹

Article Oncology

Management of Immune-Related Adverse Events in Patients Treated With Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline

Bianca D. Santomasso et al.

Summary: This guideline aims to provide guidance on the management of immune-related adverse events in patients treated with CAR T-cell therapy, developed by a multidisciplinary team based on expert consensus. Management of CAR T-cell-related toxicities includes supportive care and pharmacologic interventions, such as tocilizumab and corticosteroids, for severe symptoms.

JOURNAL OF CLINICAL ONCOLOGY (2021)

添加到收藏夹

Article Hematology

Immune reconstitution and infectious complications following axicabtagene ciloleucel therapy for large B-cell lymphoma

John H. Baird et al.

Summary: CAR T-cell therapy targeting CD19 improves outcomes in LBCL treatment, but long-term monitoring of hematologic recovery, immune reconstitution, and antimicrobial prophylaxis is necessary for patients post-treatment.

BLOOD ADVANCES (2021)

添加到收藏夹

Letter Oncology

Viral infection/reactivation during long-term follow-up in multiple myeloma patients with anti-BCMA CAR therapy

Di Wang et al.

BLOOD CANCER JOURNAL (2021)

添加到收藏夹

Article Hematology

Humoral immune reconstitution after anti-BCMA CAR T-cell therapy in relapsed/refractory multiple myeloma

Ying Wang et al.

Summary: The study revealed a significant and lasting humoral immune deficiency, especially for IgA, in patients with relapsed/refractory MM who received anti-BCMA CAR T-cell therapy.

BLOOD ADVANCES (2021)

添加到收藏夹

Letter Hematology

Macrophage activation syndrome-like (MAS-L) manifestations following BCMA-directed CAR T cells in multiple myeloma

Vanessa E. Kennedy et al.

BLOOD ADVANCES (2021)

添加到收藏夹

Article Hematology

Outcomes in patients treated with chimeric antigen receptor T-cell therapy who were admitted to intensive care (CARTTAS): an international, multicentre, observational cohort study

Élie Azoulay et al.

Lancet Haematology (2021)

添加到收藏夹

Article Hematology

CAR-HEMATOTOX: a model for CAR T-cell-related hematologic toxicity in relapsed/refractory large B-cell lymphoma

Kai Rejeski et al.

Summary: Hematotoxicity is a common adverse event in CAR T-cell therapy, with baseline thrombocytopenia and hyperferritinemia being significant predictive markers. The CAR-HEMATOTOX model can accurately predict the occurrence of severe neutropenia.

BLOOD (2021)

添加到收藏夹

Article Hematology

Characterization of HLH-like manifestations as a CRS variant in CD22 CAR T cells

Daniel A. Lichtenstein et al.

Summary: In a subset of patients with cytokine release syndrome (CRS), chimeric antigen receptor (CAR) T-cell toxicities resembling hemophagocytic lymphohistiocytosis (HLH) can occur, known as carHLH. This study comprehensively characterized the manifestations and timing of carHLH, highlighting factors such as preinfusion natural killer cell lymphopenia and higher bone marrow T-cell:NK cell ratio associated with its development. Additionally, carHLH was characterized by persistent elevation of HLH-associated inflammatory cytokines following CAR T-cell expansion.

BLOOD (2021)

添加到收藏夹

Article Hematology

Prophylactic corticosteroid use in patients receiving axicabtagene ciloleucel for large B-cell lymphoma

Olalekan O. Oluwole et al.

Summary: Prophylactic corticosteroids and earlier intervention with corticosteroids and/or tocilizumab resulted in a reduced rate of severe treatment-related toxicities and high response rates in patients with refractory large B-cell lymphoma. The majority of patients did not experience CRS or NEs within 72 hours of axi-cel treatment. Furthermore, 95% of patients achieved objective responses and 80% achieved complete responses in this study.

BRITISH JOURNAL OF HAEMATOLOGY (2021)

添加到收藏夹

Letter Hematology

Ruxolitinib for refractory/relapsed hemophagocytic lymphohistiocytosis

Jingshi Wang et al.

HAEMATOLOGICA (2020)

添加到收藏夹

Article

Intrathecal Chemotherapy: An Alternative Treatment Strategy to Prolonged Corticosteroids for Severe CAR T Associated Neurotoxicity

Filiz Yucebay et al.

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION (2020)

添加到收藏夹

Article Oncology

Standard-of-Care Axicabtagene Ciloleucel for Relapsed or Refractory Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium

Loretta J. Nastoupil et al.

JOURNAL OF CLINICAL ONCOLOGY (2020)

添加到收藏夹

Review Immunology

Diagnosis and Management of Secondary HLH/MAS Following HSCT and CAR-T Cell Therapy in Adults; A Review of the Literature and a Survey of Practice Within EBMT Centres on Behalf of the Autoimmune Diseases Working Party (ADWP) and Transplant Complications Working Party (TCWP)

Robert David Sandler et al.

FRONTIERS IN IMMUNOLOGY (2020)

添加到收藏夹

Article Medicine, General & Internal

KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma

Michael Wang et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

添加到收藏夹

Letter Biophysics

G-CSF does not worsen toxicities and efficacy of CAR-T cells in refractory/relapsed B-cell lymphoma

Eugenio Galli et al.

BONE MARROW TRANSPLANTATION (2020)

添加到收藏夹

Article Hematology

DLBCL patients treated with CD19 CAR T cells experience a high burden of organ toxicities but low nonrelapse mortality

Kitsada Wudhikarn et al.

BLOOD ADVANCES (2020)

添加到收藏夹

Editorial Material Hematology

Clinical efficacy of anakinra to mitigate CAR T-cell therapy-associated toxicity in large B-cell lymphoma

Paolo Strati et al.

BLOOD ADVANCES (2020)

添加到收藏夹

Article Hematology

Hematopoietic recovery in patients receiving chimeric antigen receptor T-cell therapy for hematologic malignancies

Tania Jain et al.

BLOOD ADVANCES (2020)

添加到收藏夹

Article Hematology

Cardiovascular Events Associated with Chimeric Antigen Receptor T Cell Therapy: Cross-Sectional FDA Adverse Events Reporting System Analysis

Avirup Guha et al.

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION (2020)

添加到收藏夹

Article Oncology

Infection during the first year in patients treated with CD19 CAR T cells for diffuse large B cell lymphoma

Kitsada Wudhikarn et al.

BLOOD CANCER JOURNAL (2020)

添加到收藏夹

Article Medicine, General & Internal

Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study

Jeremy S. Abramson et al.

LANCET (2020)

添加到收藏夹

Article Oncology

Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events

Marcela Maus et al.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2020)

添加到收藏夹

Review Clinical Neurology

Neurotoxicity-CAR T-cell therapy: what the neurologist needs to know

Lorna Neill et al.

PRACTICAL NEUROLOGY (2020)

添加到收藏夹

Review Oncology

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

Kris M. Mahadeo et al.

NATURE REVIEWS CLINICAL ONCOLOGY (2019)

添加到收藏夹

Article Hematology

Clinical presentation, management, and biomarkers of neurotoxicity after adoptive immunotherapy with CAR T cells

Philipp Karschnia et al.

BLOOD (2019)

添加到收藏夹

Article Oncology

CAR T-Cell Associated Neurotoxicity: Mechanisms, Clinicopathologic Correlates, and Future Directions

Bradley D. Hunter et al.

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE (2019)

添加到收藏夹

Article Cell Biology

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

Katrin Mestermann et al.

SCIENCE TRANSLATIONAL MEDICINE (2019)

添加到收藏夹

Review Hematology

CAR-T - and a side order of IgG, to go? - Immunoglobulin replacement in patients receiving CAR-T cell therapy

Joshua A. Hill et al.

BLOOD REVIEWS (2019)

添加到收藏夹

Article Hematology

ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells

Daniel W. Lee et al.

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION (2019)

添加到收藏夹

Article Hematology

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

Rosalie M. Sterner et al.

BLOOD (2019)

添加到收藏夹

Article Oncology

Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial

Frederick L. Locke et al.

LANCET ONCOLOGY (2019)

添加到收藏夹

Article Hematology

Pharmacologic control of CAR-T cell function using dasatinib

Evan W. Weber et al.

BLOOD ADVANCES (2019)

添加到收藏夹

Review Hematology

CAR T Cell Toxicity: Current Management and Future Directions

Lucrecia Yanez et al.

HEMASPHERE (2019)

添加到收藏夹

Review Oncology

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

Sattva S. Neelapu et al.

NATURE REVIEWS CLINICAL ONCOLOGY (2018)

添加到收藏夹

Article Biochemistry & Molecular Biology

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

Margherita Norelli et al.

NATURE MEDICINE (2018)

添加到收藏夹

Article Medicine, General & Internal

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

S. L. Maude et al.

NEW ENGLAND JOURNAL OF MEDICINE (2018)

添加到收藏夹

Article Oncology

Clinical and Biological Correlates of Neurotoxicity Associated with CAR T-cell Therapy in Patients with B-cell Acute Lymphoblastic Leukemia

Bianca D. Santomasso et al.

CANCER DISCOVERY (2018)

添加到收藏夹

Article

Cytokine Release Syndrome with Chimeric Antigen Receptor T Cell Therapy

Noelle Frey et al.

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION (2018)

添加到收藏夹

Article Clinical Neurology

Neurotoxicity Associated with CD19-Targeted CAR-T Cell Therapies

Juliane Gust et al.

CNS DRUGS (2018)

添加到收藏夹

Article Medicine, General & Internal

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

S. S. Neelapu et al.

NEW ENGLAND JOURNAL OF MEDICINE (2017)

添加到收藏夹

Article Hematology

Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor-modified T-cell therapy

Kevin A. Hay et al.

BLOOD (2017)

添加到收藏夹

Article Hematology

Ruxolitinib for treatment of refractory hemophagocytic lymphohistiocytosis

Larisa Broglie et al.

BLOOD ADVANCES (2017)

添加到收藏夹

Article Oncology

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

David T. Teachey et al.

CANCER DISCOVERY (2016)

添加到收藏夹

Article Medicine, General & Internal

Inducible Apoptosis as a Safety Switch for Adoptive Cell Therapy

Antonio Di Stasi et al.

NEW ENGLAND JOURNAL OF MEDICINE (2011)

添加到收藏夹

Article Hematology

Retroviral transfer of human CD20 as a suicide gene for adoptive T-cell therapy

Marieke Griffioen et al.

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL (2009)

添加到收藏夹

A Primer on Chimeric Antigen Receptor T-cell Therapy-related Toxicities for the Intensivist

相关参考文献

导出引文

分享论文