CD19 CAR T cells following autologous transplantation in poor-risk relapsed and refractory B-cell non-Hodgkin lymphoma Journal Article

Authors: Sauter, C. S.; Senechal, B.; Rivière, I.; Ni, A.; Bernal, Y.; Wang, X.; Purdon, T.; Hall, M.; Singh, A. N.; Szenes, V. Z.; Yoo, S.; Dogan, A.; Wang, Y.; Moskowitz, C. H.; Giralt, S.; Matasar, M. J.; Perales, M. A.; Curran, K. J.; Park, J.; Sadelain, M.; Brentjens, R. J.
Article Title: CD19 CAR T cells following autologous transplantation in poor-risk relapsed and refractory B-cell non-Hodgkin lymphoma
Abstract: High-dose chemotherapy and autologous stem cell transplantation (HDT-ASCT) is the standard of care for relapsed or primary refractory (rel/ref) chemorefractory diffuse large B-cell lymphoma. Only 50% of patients are cured with this approach. We investigated safety and efficacy of CD19-specific chimeric antigen receptor (CAR) T cells administered following HDT-ASCT. Eligibility for this study includes poor-risk rel/ref aggressive B-cell non-Hodgkin lymphoma chemosensitive to salvage therapy with: (1) positron emission tomography-positive disease or (2) bone marrow involvement. Patients underwent standard HDT-ASCT followed by 19-28z CAR T cells on days 12 and 13. Of 15 subjects treated on study, dose-limiting toxicity was observed at both dose levels (5 3 106 and 1 3 107 19-28z CAR T per kilogram). Ten of 15 subjects experienced CAR T-cell-induced neurotoxicity and/or cytokine release syndrome (CRS), which were associated with greater CAR T-cell persistence (P 5 .05) but not peak CAR T-cell expansion. Serum interferon-g elevation (P < .001) and possibly interleukin-10 (P 5 .07) were associated with toxicity. The 2-year progression-free survival (PFS) is 30% (95% confidence interval, 20% to 70%). Subjects given decreased naive-like (CD45RA1CCR71) CD41 and CD81 CAR T cells experienced superior PFS (P 5 .02 and .04, respectively). There was no association between CAR T-cell peak expansion, persistence, or cytokine changes and PFS. 19-28z CAR T cells following HDT-ASCT were associated with a high incidence of reversible neurotoxicity and CRS. Following HDT-ASCT, effector CD41 and CD81 immunophenotypes may improve disease control. This trial was registered at www. as #NCT01840566. © 2011 by The American Society of Hematology; all rights reserved.
Journal Title: Blood
Volume: 134
Issue: 7
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2019-08-15
Start Page: 626
End Page: 635
Language: English
DOI: 10.1182/blood.2018883421
PUBMED: 31262783
PROVIDER: scopus
PMCID: PMC6695562
Notes: Article -- Source: Scopus
Citation Impact
MSK Authors
  1. Craig Moskowitz
    391 Moskowitz
  2. Renier J Brentjens
    236 Brentjens
  3. Sergio Andres Giralt
    621 Giralt
  4. Kevin Joseph Curran
    74 Curran
  5. Jae Hong Park
    182 Park
  6. Craig Steven Sauter
    204 Sauter
  7. Miguel-Angel Perales
    466 Perales
  8. Matthew J Matasar
    153 Matasar
  9. Michel W J Sadelain
    491 Sadelain
  10. Isabelle C Riviere
    192 Riviere
  11. Xiuyan Wang
    87 Wang
  12. Yvette J Bernal
    29 Bernal
  13. Terence John Purdon
    49 Purdon
  14. Ahmet Dogan
    238 Dogan
  15. Victoria Zee Szenes
    12 Szenes
  16. Yongzeng   Wang
    17 Wang
  17. Ai   Ni
    84 Ni
  18. Sarah Min Kyung Yoo
    13 Yoo
  19. Malloury W Hall
    4 Hall
  20. Ashvin N Singh
    1 Singh