Cristina Gutierrez1, Anne Rain T Brown2, Heather P May3, Amer Beitinjaneh4, R Scott Stephens5, Prabalini Rajendram6, Joseph L Nates7, Stephen M Pastores8, Ananda Dharshan9, Alice Gallo de Moraes10, Matthew K Hensley11, Lei Feng12, Jennifer N Brudno13, Janhavi Athale14, Monalisa Ghosh15, James N Kochenderfer16, Alejandro S Arias17, Yi Lin18, Colleen McEvoy19, Elena Mead8, Jason Westin20, Natalie Kostelecky8, Agrima Mian21, Megan M Herr22. 1. Department of Critical Care, The University of Texas M.D. Anderson Cancer Center, Houston, TX. 2. Clinical Pharmacy Specialist in Critical Care, Division of Pharmacy, The University of Texas M.D. Anderson Cancer Center, Houston, TX. 3. Mayo Clinic College of Medicine and Science, Critical Care Clinical Pharmacist, Department of Pharmacy, Mayo Clinic, Rochester, MN. 4. Department of Medicine, Division of Transplantation and Cellular Therapy, University of Miami, Miami, FL. 5. Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD. 6. Department of Critical Care, Cleveland Clinic, Cleveland Clinic Lerner School of Medicine, Cleveland, OH. 7. Division of Anesthesiology and Critical Care, Department of Critical Care, The University of Texas M.D. Anderson Cancer Center, Houston, TX. 8. Department of Anesthesiology and Critical Care Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY. 9. Roswell Park Comprehensive Cancer Center, Department of Anesthesiology, Jacobs School of Medicine & Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY. 10. Department of Medicine, Division of Pulmonary and Critical Care, Mayo Clinic, Rochester, MN. 11. Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA. 12. Department of Statistics, The University of Texas M.D. Anderson Cancer Center, Houston, TX. 13. Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD. 14. Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, MD. 15. Department of Medicine, Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI. 16. Tenure-track Investigator, Surgery Branch of the National Cancer Institute, National Cancer Institute, National Institute of Health, Bethesda, MD. 17. Department of Pulmonary, Critical Care and Sleep Medicine, University of Miami, Miami, FL. 18. Division of Hematology, Division of Experimental Pathology, Mayo Clinic, Rochester, MN. 19. Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO. 20. Department of Lymphoma and Myeloma, The University of Texas M.D. Anderson Cancer Center, Houston, TX. 21. Department of Medicine, Cleveland Clinic, Cleveland, OH. 22. Transplant and Cellular Therapy Program, Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY.
Abstract
OBJECTIVES: To report the epidemiology, treatments, and outcomes of adult patients admitted to the ICU after cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. DESIGN: Retrospective cohort study. SETTING: Nine centers across the U.S. part of the chimeric antigen receptor-ICU initiative. PATIENTS: Adult patients treated with chimeric antigen receptor T-cell therapy who required ICU admission between November 2017 and May 2019. INTERVENTIONS: Demographics, toxicities, specific interventions, and outcomes were collected. RESULTS: One-hundred five patients treated with axicabtagene ciloleucel required ICU admission for cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome during the study period. At the time of ICU admission, the majority of patients had grade 3-4 toxicities (66.7%); 15.2% had grade 3-4 cytokine release syndrome and 64% grade 3-4 immune effector cell-associated neurotoxicity syndrome. During ICU stay, cytokine release syndrome was observed in 77.1% patients and immune effector cell-associated neurotoxicity syndrome in 84.8% of patients; 61.9% patients experienced both toxicities. Seventy-nine percent of patients developed greater than or equal to grade 3 toxicities during ICU stay, however, need for vasopressors (18.1%), mechanical ventilation (10.5%), and dialysis (2.9%) was uncommon. Immune Effector Cell-Associated Encephalopathy score less than 3 (69.7%), seizures (20.2%), status epilepticus (5.7%), motor deficits (12.4%), and cerebral edema (7.9%) were more prevalent. ICU mortality was 8.6%, with only three deaths related to cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. Median overall survival time was 10.4 months (95% CI, 6.64-not available mo). Toxicity grade or organ support had no impact on overall survival; higher cumulative corticosteroid doses were associated to decreased overall and progression-free survival. CONCLUSIONS: This is the first study to describe a multicenter cohort of patients requiring ICU admission with cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome after chimeric antigen receptor T-cell therapy. Despite severe toxicities, organ support and in-hospital mortality were low in this patient population.
OBJECTIVES: To report the epidemiology, treatments, and outcomes of adult patients admitted to the ICU after cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. DESIGN: Retrospective cohort study. SETTING: Nine centers across the U.S. part of the chimeric antigen receptor-ICU initiative. PATIENTS: Adult patients treated with chimeric antigen receptor T-cell therapy who required ICU admission between November 2017 and May 2019. INTERVENTIONS: Demographics, toxicities, specific interventions, and outcomes were collected. RESULTS: One-hundred five patients treated with axicabtagene ciloleucel required ICU admission for cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome during the study period. At the time of ICU admission, the majority of patients had grade 3-4 toxicities (66.7%); 15.2% had grade 3-4 cytokine release syndrome and 64% grade 3-4 immune effector cell-associated neurotoxicity syndrome. During ICU stay, cytokine release syndrome was observed in 77.1% patients and immune effector cell-associated neurotoxicity syndrome in 84.8% of patients; 61.9% patients experienced both toxicities. Seventy-nine percent of patients developed greater than or equal to grade 3 toxicities during ICU stay, however, need for vasopressors (18.1%), mechanical ventilation (10.5%), and dialysis (2.9%) was uncommon. Immune Effector Cell-Associated Encephalopathy score less than 3 (69.7%), seizures (20.2%), status epilepticus (5.7%), motor deficits (12.4%), and cerebral edema (7.9%) were more prevalent. ICU mortality was 8.6%, with only three deaths related to cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. Median overall survival time was 10.4 months (95% CI, 6.64-not available mo). Toxicity grade or organ support had no impact on overall survival; higher cumulative corticosteroid doses were associated to decreased overall and progression-free survival. CONCLUSIONS: This is the first study to describe a multicenter cohort of patients requiring ICU admission with cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome after chimeric antigen receptor T-cell therapy. Despite severe toxicities, organ support and in-hospital mortality were low in this patient population.
Authors: Frederick L Locke; Armin Ghobadi; Caron A Jacobson; David B Miklos; Lazaros J Lekakis; Olalekan O Oluwole; Yi Lin; Ira Braunschweig; Brian T Hill; John M Timmerman; Abhinav Deol; Patrick M Reagan; Patrick Stiff; Ian W Flinn; Umar Farooq; Andre Goy; Peter A McSweeney; Javier Munoz; Tanya Siddiqi; Julio C Chavez; Alex F Herrera; Nancy L Bartlett; Jeffrey S Wiezorek; Lynn Navale; Allen Xue; Yizhou Jiang; Adrian Bot; John M Rossi; Jenny J Kim; William Y Go; Sattva S Neelapu Journal: Lancet Oncol Date: 2018-12-02 Impact factor: 41.316
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