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


Authors: Wudhikarn, K.; Pennisi, M.; Garcia-Recio, M.; Flynn, J. R.; Afuye, A.; Silverberg, M. L.; Maloy, M. A.; Devlin, S. M.; Batlevi, C. L.; Shah, G. L.; Scordo, M.; Palomba, M. L.; Dahi, P. B.; Sauter, C. S.; Santomasso, B. D.; Mead, E.; Perales, M. A.
Article Title: DLBCL patients treated with CD19 CAR T cells experience a high burden of organ toxicities but low nonrelapse mortality
Abstract: Cytokine release syndrome (CRS) immune effector cell-associated neurotoxicity syndrome are the most notable toxicities of CD19 chimeric antigen receptor (CAR) T-cell therapy. In addition, CAR T-cell-mediated toxicities can involve any organ system, with varied impacts on outcomes, depending on patient factors and involved organs. We performed detailed analysis of organ-specific toxicities and their association with outcomes in 60 patients with diffuse large B-cell lymphoma (DLBCL) treated with CD19 CAR T cells by assessing all toxicities in organ-based groups during the first year posttreatment. We observed 539 grade $2 and 289 grade $3 toxicities. Common grade $3 toxicities included hematological, metabolic, infectious, and neurological complications, with corresponding 1-year cumulative incidence of 57.7%, 54.8%, 35.4%, and 18.3%, respectively. Patients with impaired performance status had a higher risk of grade $3 metabolic complications, whereas elevated lactate dehydrogenase was associated with higher risks of grade $3 neurological and pulmonary toxicities. CRS was associated with higher incidence of grade $3 metabolic, pulmonary, and neurologic complications. The 1-year nonrelapse mortality and overall survival were 1.7% and 69%, respectively. Only grade $3 pulmonary toxicities were associated with an increased mortality risk. In summary, toxicity burdens after CD19 CAR T-cell therapy were high and varied by organ systems. Most toxicities were manageable and were rarely associated with mortality. Our study emphasizes the importance of toxicity assessment, which could serve as a benchmark for further research to reduce symptom burdens and improve tolerability in patients treated with CAR T cells. © 2020 American Society of Hematology. All rights reserved.
Keywords: adult; treatment outcome; aged; major clinical study; overall survival; constipation; neutropenia; diarrhea; heart left ventricle failure; hypertension; hypophosphatemia; disease association; esophagitis; leukopenia; thrombocytopenia; vomiting; incidence; kidney failure; food and drug administration; retrospective study; cancer mortality; febrile neutropenia; hyperglycemia; pneumonia; lung embolism; allergic rhinitis; confusion; hypoalbuminemia; hyponatremia; hypotension; insomnia; depression; pancreatitis; pleura effusion; cognitive defect; lactate dehydrogenase; seizure; headache; high risk population; aphasia; portal vein thrombosis; personal experience; pericardial effusion; atrial fibrillation; cytopenia; lactate dehydrogenase blood level; heart ventricle arrhythmia; anus fistula; hypocalcemia; cytokine release syndrome; diffuse large b cell lymphoma; influenza a; disease burden; human; male; female; priority journal; article; mortality risk; tisagenlecleucel t; axicabtagene ciloleucel; fulminant hepatic failure; however, most toxicities are manageable and rarely cause mortality. , a uniform toxicity assessment is crucial for monitoring adverse events and improving experience in patients receiving cd19 car t cells; toxicity burdens in dlbcl patients treated with car t cells are high
Journal Title: Blood Advances
Volume: 4
Issue: 13
ISSN: 2473-9529
Publisher: American Society of Hematology  
Date Published: 2020-07-14
Start Page: 3024
End Page: 3033
Language: English
DOI: 10.1182/bloodadvances.2020001972
PUBMED: 32614964
PROVIDER: scopus
PMCID: PMC7362382
DOI/URL:
Notes: Article -- Export Date: 3 August 2020 -- Source: Scopus
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MSK Authors
  1. Maria Lia Palomba
    176 Palomba
  2. Craig Steven Sauter
    210 Sauter
  3. Miguel-Angel Perales
    494 Perales
  4. Molly Anna Maloy
    191 Maloy
  5. Sean McCarthy Devlin
    378 Devlin
  6. Parastoo Bahrami Dahi
    138 Dahi
  7. Michael Scordo
    91 Scordo
  8. Connie Wing-Ching Lee
    76 Lee
  9. Gunjan Lalitchandra Shah
    132 Shah
  10. Elena   Mead
    30 Mead
  11. Aishat Olaide Afuye
    7 Afuye
  12. Jessica Flynn
    49 Flynn
  13. Martina Pennisi
    12 Pennisi