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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