Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia Journal Article

Authors: Davila, M. L.; Riviere, I.; Wang, X.; Bartido, S.; Park, J.; Curran, K.; Chung, S. S.; Stefanski, J.; Borquez-Ojeda, O.; Olszewska, M.; Qu, J.; Wasielewska, T.; He, Q.; Fink, M.; Shinglot, H.; Youssif, M.; Satter, M.; Wang, Y.; Hosey, J.; Quintanilla, H.; Halton, E.; Bernal, Y.; Bouhassira, D. C. G.; Arcila, M. E.; Gonen, M.; Roboz, G. J.; Maslak, P.; Douer, D.; Frattini, M. G.; Giralt, S.; Sadelain, M.; Brentjens, R.
Article Title: Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia
Abstract: We report on 16 patients with relapsed or refractory B cell acute lymphoblastic leukemia (B-ALL) that we treated with autologous T cells expressing the 19-28z chimeric antigen receptor (CAR) specific to the CD19 antigen. The overall complete response rate was 88%, which allowed us to transition most of these patients to a standard-of-care allogeneic hematopoietic stem cell transplant (allo-SCT). This therapy was as effective in high-risk patients with Philadelphia chromosome-positive (Ph+) disease as in those with relapsed disease after previous allo-SCT. Through systematic analysis of clinical data and serum cytokine levels over the first 21 days after T cell infusion, we have defined diagnostic criteria for a severe cytokine release syndrome (sCRS), with the goal of better identifying the subset of patients who will likely require therapeutic intervention with corticosteroids or interleukin-6 receptor blockade to curb the sCRS. Additionally, we found that serum C-reactive protein, a readily available laboratory study, can serve as a reliable indicator for the severity of the CRS. Together, our data provide strong support for conducting a multicenter phase 2 study to further evaluate 19-28z CAR T cells in B-ALL and a road map for patient management at centers now contemplating the use of CAR T cell therapy.
Journal Title: Science Translational Medicine
Volume: 6
Issue: 224
ISSN: 1946-6234
Publisher: American Association for the Advancement of Science  
Date Published: 2014-02-19
Start Page: 224ra25
Language: English
DOI: 10.1126/scitranslmed.3008226
PROVIDER: scopus
PUBMED: 24553386
PMCID: PMC4684949
Notes: Export Date: 2 April 2014 -- Source: Scopus
Citation Impact
MSK Authors
  1. Renier J Brentjens
    233 Brentjens
  2. Mithat Gonen
    779 Gonen
  3. Sergio Andres Giralt
    616 Giralt
  4. Kevin Joseph Curran
    73 Curran
  5. Jae Hong Park
    178 Park
  6. Stephen Shiu-Wah Chung
    59 Chung
  7. Marco Luis Davila
    24 Davila
  8. Elizabeth F Halton
    35 Halton
  9. Michel W J Sadelain
    486 Sadelain
  10. Isabelle C Riviere
    189 Riviere
  11. Peter Maslak
    182 Maslak
  12. Xiuyan Wang
    84 Wang
  13. Maria Eugenia Arcila
    459 Arcila
  14. Dan Douer
    84 Douer
  15. Shirley M Bartido
    36 Bartido
  16. James Hosey
    3 Hosey
  17. Qing He
    10 He
  18. Yvette J Bernal
    29 Bernal
  19. Mitsu J Fink
    2 Fink
  20. Jinrong Qu
    14 Qu
  21. Yongzeng   Wang
    17 Wang
  22. Mark Thomas Satter
    1 Satter