Efficacy and Toxicity Management of 19-28z CAR T Cell Therapy in B Cell Acute Lymphoblastic Leukemia

Sci Transl Med 19 February 2014: 
Vol. 6, Issue 224, p. 224ra25 
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3008226

• RESEARCH ARTICLE

CANCER

Efficacy and Toxicity Management of 19-28z CAR T Cell Therapy in B Cell Acute Lymphoblastic Leukemia

1. Marco L. Davila1, 
2. Isabelle Riviere1,2,3,4, 
3. Xiuyan Wang4, 
4. Shirley Bartido4, 
5. Jae Park1, 
6. Kevin Curran5,
7. Stephen S. Chung1, 
8. Jolanta Stefanski4, 
9. Oriana Borquez-Ojeda4, 
10. Malgorzata Olszewska4, 
11. Jinrong Qu4,
12. Teresa Wasielewska4, 
13. Qing He4, 
14. Mitsu Fink4, 
15. Himaly Shinglot4, 
16. Maher Youssif4, 
17. Mark Satter4,
18. Yongzeng Wang4, 
19. James Hosey4, 
20. Hilda Quintanilla1, 
21. Elizabeth Halton1, 
22. Yvette Bernal1,
23. Diana C. G. Bouhassira2, 
24. Maria E. Arcila6, 
25. Mithat Gonen7, 
26. Gail J. Roboz8, 
27. Peter Maslak1, 
28. Dan Douer1,
29. Mark G. Frattini9, 
30. Sergio Giralt1,2, 
31. Michel Sadelain1,2,3,* and 
32. Renier Brentjens1,2,3,*

+Author Affiliations

1. ¹Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
2. ²Center for Cell Engineering, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
3. ³Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
4. ⁴Cell Therapy and Cell Engineering Facility, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
5. ⁵Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
6. ⁶Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
7. ⁷Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
8. ⁸Leukemia Service, NewYork-Presbyterian/Weill Cornell, New York, NY 10065, USA.
9. ⁹Leukemia Service, NewYork-Presbyterian/Columbia, New York, NY 10032, USA.

1. ↵*Corresponding author. E-mail: brentjer@mskcc.org (R.B.); m-sadelain@ski.mskcc.org (M.S.)

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.

• Copyright © 2014, American Association for the Advancement of Science

Citation: M. L. Davila, I. Riviere, X. Wang, S. Bartido, J. Park, K. Curran, S. S. Chung, J. Stefanski, O. Borquez-Ojeda, M. Olszewska, J. Qu, T. Wasielewska, Q. He, M. Fink, H. Shinglot, M. Youssif, M. Satter, Y. Wang, J. Hosey, H. Quintanilla, E. Halton, Y. Bernal, D. C. Bouhassira, M. E. Arcila, M. Gonen, G. J. Roboz, P. Maslak, D. Douer, M. G. Frattini, S. Giralt, M. Sadelain, R. Brentjens, Efficacy and Toxicity Management of 19-28z CAR T Cell Therapy in B Cell Acute Lymphoblastic Leukemia. Sci. Transl. Med. 6, 224ra25 (2014).

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