Comparing CAR T-cell toxicity grading systems: Application of the ASTCT grading system and implications for management Journal Article


Authors: Pennisi, M.; Jain, T.; Santomasso, B. D.; Mead, E.; Wudhikarn, K.; Silverberg, M. L.; Batlevi, Y.; Shouval, R.; Devlin, S. M.; Batlevi, C.; Brentjens, R. J.; Dahi, P. B.; Diamonte, C.; Giralt, S.; Halton, E. F.; Maloy, M.; Palomba, M. L.; Sanchez-Escamilla, M.; Sauter, C. S.; Scordo, M.; Shah, G.; Park, J. H.; Perales, M. A.
Article Title: Comparing CAR T-cell toxicity grading systems: Application of the ASTCT grading system and implications for management
Abstract: Various grading systems are currently used for chimeric antigen receptor (CAR) T-cell-related toxicity, cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS).We compared the recently proposed American Society for Transplantation and Cellular Therapy (ASTCT) grading system to other grading scores in 2 populations of adults: Patients (n = 53) with B-cell acute lymphoblastic leukemia (B-ALL) treated with 1928z CAR T-cells (clinicaltrials.gov #NCT01044069), and patients (n = 49) with diffuse large B-cell lymphoma (DLBCL) treated with axicabtagene-ciloleucel (axi-cel) or tisagenlecleucel after US Food and DrugAdministration approval. According to ASTCT grading, 82%of patients had CRS, 87% in the B-ALL and 77% in the DLBCL groups (axi-cel: 86%, tisagenlecleucel: 54%), whereas 50% of patients experienced ICANS, 55% in the B-ALL and 45% in the DLBCL groups (axi-cel: 55%, tisagenlecleucel: 15%). All grading systems agreed on CRS and ICANS diagnosis in 99% and 91%of cases, respectively. However,when analyzed grade by grade, only 25%and 54%of patients had the same grade in each system for CRS and ICANS, respectively, as different systems score symptoms differently (upgrading or downgrading their severity), leading to inconsistent final grades. Investigation of possible management implications in DLBCL patients showed that different recommendations on tocilizumab and steroids across current guidelines potentially result in either overtreating or delaying treatment. Moreover, because these guidelines are based on single products and different grading systems, they cannot be universally applied. To avoid discrepancies in assessing and managing toxicities of different products,we propose that unified grading be used across clinical trials and in practice and that paired management guidelines with product-specific indications be developed. © 2020 by The American Society of Hematology.
Journal Title: Blood Advances
Volume: 4
Issue: 4
ISSN: 2473-9529
Publisher: American Society of Hematology  
Date Published: 2020-02-25
Start Page: 676
End Page: 686
Language: English
DOI: 10.1182/bloodadvances.2019000952
PUBMED: 32084260
PROVIDER: scopus
PMCID: PMC7042979
DOI/URL:
Notes: Article -- Source: Scopus
Altmetric
Citation Impact
MSK Authors
  1. Renier J Brentjens
    233 Brentjens
  2. Maria Lia Palomba
    165 Palomba
  3. Sergio Andres Giralt
    613 Giralt
  4. Jae Hong Park
    178 Park
  5. Craig Steven Sauter
    199 Sauter
  6. Miguel-Angel Perales
    455 Perales
  7. Elizabeth F Halton
    35 Halton
  8. Molly Anna Maloy
    170 Maloy
  9. Sean McCarthy Devlin
    353 Devlin
  10. Parastoo Bahrami Dahi
    124 Dahi
  11. Michael Scordo
    76 Scordo
  12. Connie Wing-Ching Lee
    69 Lee
  13. Gunjan Lalitchandra Shah
    116 Shah
  14. Elena   Mead
    26 Mead
  15. Tania Jain
    13 Jain