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Cited by 216CAR-T cell therapy researchAutoimmune and Inflammatory Disorders ResearchCancer Immunotherapy and Biomarkers

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Cytokine release syndrome and neurotoxicity following CAR T-cell therapy for hematologic malignancies

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Freyer, Craig W., Porter, David L.·2020·Journal of Allergy and Clinical Immunology
DOI 10.1016/j.jaci.2020.07.025
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Abstract

Chimeric antigen receptor T cells are a new and exciting immunotherapeutic approach to managing cancer, with impressive efficacy but potentially life-threatening inflammatory toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Patients with severe CRS may develop capillary leak syndrome and disseminated intravascular coagulation, with a cytokine signature similar to that of macrophage activation syndrome/hemophagocytic lymphohistiocytosis. Moderate-to-severe CRS is managed with the IL-6 receptor antagonist tocilizumab with or without corticosteroids, with questions remaining regarding the optimal management of nonresponders. ICANS is an inflammatory neurotoxicity typically occurring after CRS and characterized by impaired blood-brain barrier integrity. Symptoms of encephalopathy range from mild confusion and aphasia to somnolence, obtundation, and in some cases seizures and cerebral edema. ICANS is currently managed with corticosteroids; however, the optimal dose and duration remain to be determined. Little information is available to guide the management of patients with steroid-refractory ICANS. Numerous cytokine-targeted therapies have been proposed to manage these inflammatory toxicities, but few clinical data are available. Management of inflammatory toxicities of chimeric antigen receptor T cells often requires multidisciplinary management and intensive care, during which allergists and immunologists may…

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Research works printed but not linked: 49

  1. Loren, 2008, Donor leukocyte infusions for the treatment of relapsed acute leukemia after allogeneic stem cell transplantation, Bone Marrow Transplant, 41, 483, 10.1038/sj.bmt.1705898 · DOI
  2. Fesnak, 2016, Engineered T cells: the promise and challenges of cancer immunotherapy, Nat Rev Cancer, 16, 566, 10.1038/nrc.2016.97 · DOI · Paper page
  3. June, 2018, Chimeric antigen receptor therapy, New Engl J Med, 379, 64, 10.1056/NEJMra1706169 · DOI
  4. Gill, 2016, Chimeric antigen receptor T cell therapy: 25 years in the making, Blood Rev, 30, 157, 10.1016/j.blre.2015.10.003 · DOI
  5. Kenderian, 2017, Chimeric antigen receptor T cells and hematopoietic cell transplantation: how not to put the CART before the horse, Biol Blood Marrow Transplant, 23, 235, 10.1016/j.bbmt.2016.09.002 · DOI
  6. Frey, 2016, CAR T-cells merge into the fast lane of cancer care, Am J Hematol, 91, 146, 10.1002/ajh.24238 · DOI
  7. Witzens-Harig, 2014, Maintenance rituximab is safe and not associated with severe or uncommon infections in patients with follicular lymphoma: results from the phase IIIB MAXIMA study, Ann Hematol, 93, 1714
  8. Zugmaier, 2014, Long-term follow-up of serum immunoglobulin levels in blinatumomab-treated patients with minimal residual disease-positive B-precursor acute lymphoblastic leukemia, Blood Cancer J, 4, 244, 10.1038/bcj.2014.64 · DOI
  9. Hunger, 2012, Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the Children’s Oncology Group, J Clin Oncol, 30, 1663, 10.1200/JCO.2011.37.8018 · DOI
  10. Nguyen, 2008, Factors influencing survival after relapse from acute lymphoblastic leukemia: a Children’s Oncology Group Study, Leukemia, 22, 2142, 10.1038/leu.2008.251 · DOI
  11. Crump, 2017, Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study, Blood, 130, 1800, 10.1182/blood-2017-03-769620 · DOI
  12. Neelapu, 2017, Axicabtagene ciloleucel CAR T-cell therapy in refractory Large B-cell lymphoma, New Engl J Med, 377, 2531, 10.1056/NEJMoa1707447 · DOI · Paper page
  13. Lee, 2014, Current concepts in the diagnosis and management of cytokine release syndrome, Blood, 124, 188, 10.1182/blood-2014-05-552729 · DOI · Paper page
  14. Frey, 2019, Cytokine release syndrome with chimeric antigen receptor T cell therapy, Biol Blood Marrow Transplant, 25, e123, 10.1016/j.bbmt.2018.12.756 · DOI
  15. Hay, 2018, Cytokine release syndrome and neurotoxicity after CD19 chimeric antigen receptor-modified T cell therapy, Br J Haematol, 183, 364, 10.1111/bjh.15644 · DOI
  16. Jiang, 2019, Improving the safety of CAR-T cell therapy by controlling CRS-related coagulopathy, Ann Hematol, 98, 1721, 10.1007/s00277-019-03685-z · DOI
  17. Buechner, 2017, Management of coagulopathy associated with CTL019 CAR T-cell therapy, Blood, 130, 1276
  18. Alvi, 2019, Cardiovascular events among adults treated with chimeric antigen receptor T-cells (CAR-T), J Am Coll Cardiol, 74, 3099, 10.1016/j.jacc.2019.10.038 · DOI
  19. Fitzgerald, 2017, Cytokine release syndrome after chimeric antigen receptor T cell therapy for acute lymphoblastic leukemia, Crit Care Med, 45, e124, 10.1097/CCM.0000000000002053 · DOI
  20. Hay, 2017, Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor-modified T-cell therapy, Blood, 130, 2295, 10.1182/blood-2017-06-793141 · DOI · Paper page
  21. Fried, 2019, Early and late hematologic toxicity following CD19 CAR-T cells, Bone Marrow Transplant, 54, 1643, 10.1038/s41409-019-0487-3 · DOI
  22. Hill, 2018, Infectious complications of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy, Blood, 131, 121, 10.1182/blood-2017-07-793760 · DOI
  23. Park, 2018, Cytokine release syndrome grade as a predictive marker for infections in patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with chimeric antigen receptor T cells, Clin Infect Dis, 67, 533, 10.1093/cid/ciy152 · DOI
  24. Frey, 2020, Optimizing chimeric antigen receptor T-cell therapy for adults with acute lymphoblastic leukemia, J Clin Oncol, 38, 415, 10.1200/JCO.19.01892 · DOI
  25. Singh, 2017, Monocyte lineage-derived IL-6 does not affect chimeric antigen receptor T-cell function, Cytotherapy, 19, 867, 10.1016/j.jcyt.2017.04.001 · DOI · Paper page
  26. Cox, 2020, Improved anti-tumor response of chimeric antigen receptor T cell (CART) therapy after GM-CSF inhibition is mechanistically supported by a novel direct interaction of GM-CSF with activated Carts, Biol Blood Marrow Transplant, 26, S60, 10.1016/j.bbmt.2019.12.227 · DOI
  27. Gofshteyn, 2018, Neurotoxicity after CTL019 in a pediatric and young adult cohort, Ann Neurol, 84, 537, 10.1002/ana.25315 · DOI
  28. Santomasso, 2018, Clinical and biological correlates of neurotoxicity associated with CAR T-cell therapy in patients with B-cell acute lymphoblastic leukemia, Cancer Discov, 8, 958, 10.1158/2159-8290.CD-17-1319 · DOI · Paper page
  29. Gust, 2017, Endothelial activation and blood-brain barrier disruption in neurotoxicity after adoptive immunotherapy with CD19 CAR-T cells, Cancer Discov, 7, 1, 10.1158/2159-8290.CD-17-0698 · DOI · Paper page
  30. Davila, 2014, Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia, Sci Transl Med, 6, 224ra25, 10.1126/scitranslmed.3008226 · DOI
  31. Porter, 2018, Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel, J Hematol Oncol, 11, 35, 10.1186/s13045-018-0571-y · DOI
  32. Lee, 2019, ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells, Biol Blood Marrow Transplant, 25, 625, 10.1016/j.bbmt.2018.12.758 · DOI · Paper page
  33. Locke, 2017, Preliminary results of prophylactic tocilizumab after axicabtagene ciloleucel (axi-cel; KTE-C19) treatment for patients with refractory, aggressive, non-Hodgkin lymphoma (NHL), Blood, 130, 1547, 10.1182/blood.V130.Suppl_1.1547.1547 · DOI
  34. Ahmed, 2020, Prophylactic tocilizumab in patients with relapsed refractory lymphoma treated with anti CD19 chimeric antigen receptor T cell therapy, Biol Blood Marrow Transplant, 26, S275, 10.1016/j.bbmt.2019.12.447 · DOI
  35. Myers, 2020, Risk-adapted tocilizumab decreases severe cytokine release syndrome (CRS) after CTL019 CD19-targeted chimeric antigen receptor (CAR) T-cell therapy for pediatric B-cell acute lymphoblastic leukemia (B-ALL), Biol Blood Marrow Transplant, 26, S39, 10.1016/j.bbmt.2019.12.105 · DOI
  36. Park, 2020, 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), Biol Blood Marrow Transplant, 26, S269, 10.1016/j.bbmt.2019.12.436 · DOI
  37. Sterner, 2019, GM-CSF inhibition reduces cytokine release syndrome and neuroinflammation but enhances CAR-T cell function in xenografts, Blood, 133, 697, 10.1182/blood-2018-10-881722 · DOI
  38. Neelapu, 2018, Chimeric antigen receptor T-cell therapy – assessment and management of toxicities, Nat Rev Clin Oncol, 15, 47, 10.1038/nrclinonc.2017.148 · DOI · Paper page
  39. Teachey, 2018, Toxicity management after chimeric antigen receptor T cell therapy: one size does not fit ‘ALL’, Nat Rev Clin Oncol, 15, 218, 10.1038/nrclinonc.2018.19 · DOI
  40. Le, 2018, FDA approval summary: tocilizumab for treatment of chimeric antigen receptor T cell-induced severe or life-threatening cytokine release syndrome, Oncologist, 23, 943, 10.1634/theoncologist.2018-0028 · DOI
  41. Gardner, 2019, Preemptive mitigation of CD19 CAR T-cell cytokine release syndrome without attenuation of antileukemic efficacy, Blood, 134, 2419, 10.1182/blood.2019001463 · DOI
  42. Liu, 2019, Corticosteroids do not influence the efficacy and kinetics of CAR-T cells for B-cell acute lymphoblastic leukemia, Blood, 134, 228, 10.1182/blood-2019-123051 · DOI
  43. Topp, 2020, Earlier steroid use with axicabtagene ciloleucel (axi-cel) in patients with relapsed/refractory large B cell lymphoma (R/R LBCL), Biol Blood Marrow Transplant, 26, S101, 10.1016/j.bbmt.2019.12.603 · DOI
  44. Weber, 2019, Pharmacologic control of CAR-T function using dasatinib, Blood Adv, 3, 711, 10.1182/bloodadvances.2018028720 · DOI
  45. Ahmed, 2019, Ruxolitinib in adult patients with secondary haemophagocytic lymphohistiocytosis: an open label, single-centre, pilot trial, Lancet Haematol, 6, e630, 10.1016/S2352-3026(19)30156-5 · DOI
  46. Karschnia, 2019, Clinical presentation, management, and biomarkers of neurotoxicity after adoptive immunotherapy with CAR T cells, Blood, 133, 2212, 10.1182/blood-2018-12-893396 · DOI
  47. DeAngelo, 2017, Clinical outcomes for the phase 2, single-arm, multicenter trial of JCAR015 in adult B-ALL (ROCKET Study), J Immunother Cancer, 5, P217
  48. Ruark, 2020, Patient-reported neuropsychiatric outcomes of long-term survivors after chimer antigen receptor T cell therapy, Biol Blood Marrow Transplant, 26, 34, 10.1016/j.bbmt.2019.09.037 · DOI
  49. Brudno, 2020, Safety and feasibility of anti-CD19 CAR T cells with fully human binding domains in patients with B-cell lymphoma, Nat Med, 26, 270, 10.1038/s41591-019-0737-3 · DOI

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Metadata

Authors
Freyer, C. W., & Porter, D. L.
Affiliations
Hospital of the University of Pennsylvania (US)
ORCID
Venue
Journal of Allergy and Clinical Immunology
Publisher
Elsevier BV
Published
2020-11
Volume
146
Issue
5
Pages
940-948
ISSN
0091-6749 (ISSN-L)
DOI
10.1016/j.jaci.2020.07.025
OpenAlex
W3047493249
Cited by
216
References
0
Citations by year
2026: 40 · 2025: 63 · 2024: 39 · 2023: 37 · 2022: 23 · 2021: 13 · 2020: 1
FWCI
1.99
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Allergy and Clinical Immunology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › CAR-T cell therapy research
  • Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords
cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, CAR T-cell therapy, hematologic malignancies, capillary leak syndrome, disseminated intravascular coagulation, hemophagocytic lymphohistiocytosis, tocilizumab, corticosteroids, blood-brain barrier integrity, encephalopathy, cytokine-targeted therapy, immunotherapy toxicity management
MeSH terms
Cytokine Release Syndrome, Interleukin-6 Inhibitors, Adrenal Cortex Hormones, Humans, Interleukin-6, Immunotherapy, Adoptive, Hematologic Neoplasms, Cancer Vaccines, Neurotoxicity Syndromes, Antibodies, Monoclonal, Humanized, Drug-Related Side Effects and Adverse Reactions

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