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

Marco L. Davila, Isabelle Riviere, Xiuyan Wang, Shirley Bartido, Jae Park, Kevin Curran, Stephen S. Chung, Jolanta Stefanski, Oriana Borquez-Ojeda, Malgorzata Olszewska, Jinrong Qu, Teresa Wasielewska, Qing He, Mitsu Fink, Himaly Shinglot, Maher Youssif, Mark Satter, Yongzeng Wang, James Hosey, Hilda QuintanillaElizabeth Halton, Yvette Bernal, Diana C.G. Bouhassira, Maria E. Arcila, Mithat Gonen, Gail J. Roboz, Peter Maslak, Dan Douer, Mark G. Frattini, Sergio Giralt, Michel Sadelain, Renier Brentjens

Research output: Contribution to journalArticle

1224 Scopus citations

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.

Original languageEnglish (US)
Article number224ra25
JournalScience Translational Medicine
Volume6
Issue number224
DOIs
StatePublished - Feb 19 2014
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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    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., ... Brentjens, R. (2014). Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Science Translational Medicine, 6(224), [224ra25]. https://doi.org/10.1126/scitranslmed.3008226