Cristina Gutierrez1, Anne Rain T Brown2, Megan M Herr3, Sameer S Kadri4, Brian Hill5, Prabalini Rajendram6, Abhijit Duggal7, Cameron J Turtle8, Kevin Patel9, Yi Lin10, Heather P May11, Alice Gallo de Moraes12, Marcela V Maus13, Mathew J Frigault13, Jennifer N Brudno14, Janhavi Athale4, Nirali N Shah15, James N Kochenderfer16, Ananda Dharshan17, Amer Beitinjaneh18, Alejandro S Arias19, Colleen McEvoy20, Elena Mead21, R Scott Stephens22, Joseph L Nates23, Sattva S Neelapu24, Stephen M Pastores25. 1. Department of Critical Care, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States of America. Electronic address: CGutierrez4@mdanderson.org. 2. Clinical Pharmacy Specialist in Critical Care, Department of Pharmacy, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States of America. 3. Transplant and Cellular Therapy Program, Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States of America. 4. Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, MD, United States of America. 5. Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH, United States of America. 6. Department of Critical Care, Cleveland Clinic, Cleveland Clinic Lerner School of Medicine, Cleveland, OH, United States of America. 7. Medical Intensive Care Unit, Cleveland Clinic and Assistant Professor of Medicine, Lerner School of Medicine, Cleveland Clinic, Cleveland, OH, United States of America. 8. Anderson Family Endowed Chair for Immunotherapy, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, United States of America. 9. Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle Cancer Alliance, Seattle, WA, United States of America. 10. Division of Hematology, Division of Experimental Pathology, Mayo Clinic, Rochester, MN, United States of America. 11. Mayo Clinic College of Medicine and Science, Critical Care Clinical Pharmacist, Department of Pharmacy, Mayo Clinic, Rochester, MN, United States of America. 12. Department of Medicine, Division of Pulmonary and Critical Care, Mayo Clinic, Rochester, MN, United States of America. 13. Cellular Immunotherapy Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America. 14. Assistant Research Physician, Surgery Branch, National Cancer Institute, National Institutes of Health, United States of America. 15. Pediatric Oncology Branch, National Cancer Institute, National Institute of Health, United States of America. 16. Surgery Branch of the National Cancer Institute, National Cancer Institute, National Institute of Health, United States of America. 17. Intensive Care Unit, Roswell Park Comprehensive Cancer Center, Department of Anesthesiology, Jacobs School of Medicine & Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, United States of America. 18. Department of Medicine, Division of Transplantation and Cellular Therapy, University of Miami, Miami, FL, United States of America. 19. Department of Pulmonary, Critical Care and Sleep Medicine, University of Miami, Miami, FL, United States of America. 20. Stem Cell Transplant and Oncology Intensive Care Unit, Assistant Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO, United States of America. 21. Department of Anesthesiology and Critical Care Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, United States of America. 22. Oncology and Bone Marrow Transplant Critical Care, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, United States of America. 23. Surgical and Medical Intensive Care Units, Division of Anesthesiology and Critical Care, Department of Critical Care, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States of America. 24. Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America. 25. Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, United States of America.
Abstract
PURPOSE: A task force of experts from 11 United States (US) centers, sought to describe practices for managing chimeric antigen receptor (CAR) T-cell toxicity in the intensive care unit (ICU). MATERIALS AND METHODS: Between June-July 2019, a survey was electronically distributed to 11 centers. The survey addressed: CAR products, toxicities, targeted treatments, management practices and interventions in the ICU. RESULTS: Most centers (82%) had experience with commercial and non-FDA approved CAR products. Criteria for ICU admission varied between centers for patients with Cytokine Release Syndrome (CRS) but were similar for Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS). Practices for vasopressor support, neurotoxicity and electroencephalogram monitoring, use of prophylactic anti-epileptic drugs and tocilizumab were comparable. In contrast, fluid resuscitation, respiratory support, methods of surveillance and management of cerebral edema, use of corticosteroid and other anti-cytokine therapies varied between centers. CONCLUSIONS: This survey identified areas of investigation that could improve outcomes in CAR T-cell recipients such as fluid and vasopressor selection in CRS, management of respiratory failure, and less common complications such as hemophagocytic lymphohistiocytosis, infections and stroke. The variability in specific treatments for CAR T-cell toxicities, needs to be considered when designing future outcome studies of critically ill CAR T-cell patients.
PURPOSE: A task force of experts from 11 United States (US) centers, sought to describe practices for managing chimeric antigen receptor (CAR) T-cell toxicity in the intensive care unit (ICU). MATERIALS AND METHODS: Between June-July 2019, a survey was electronically distributed to 11 centers. The survey addressed: CAR products, toxicities, targeted treatments, management practices and interventions in the ICU. RESULTS: Most centers (82%) had experience with commercial and non-FDA approved CAR products. Criteria for ICU admission varied between centers for patients with Cytokine Release Syndrome (CRS) but were similar for Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS). Practices for vasopressor support, neurotoxicity and electroencephalogram monitoring, use of prophylactic anti-epileptic drugs and tocilizumab were comparable. In contrast, fluid resuscitation, respiratory support, methods of surveillance and management of cerebral edema, use of corticosteroid and other anti-cytokine therapies varied between centers. CONCLUSIONS: This survey identified areas of investigation that could improve outcomes in CAR T-cell recipients such as fluid and vasopressor selection in CRS, management of respiratory failure, and less common complications such as hemophagocytic lymphohistiocytosis, infections and stroke. The variability in specific treatments for CAR T-cell toxicities, needs to be considered when designing future outcome studies of critically ill CAR T-cell patients.
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