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.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Marco L
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authors.lastname: Davila
authors.forename: Isabelle
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authors.lastname: Shinglot
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authors.lastname: Youssif
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authors.lastname: Satter
authors.forename: Yongzeng
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authors.lastname: Wang
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authors.lastname: Hosey
authors.forename: Hilda
authors.initials: H
authors.lastname: Quintanilla
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authors.forename: Yvette
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authors.lastname: Bernal
authors.forename: Diana C G
authors.initials: DC
authors.lastname: Bouhassira
authors.forename: Maria E
authors.initials: ME
authors.lastname: Arcila
authors.forename: Mithat
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authors.lastname: Gonen
authors.forename: Gail J
authors.initials: GJ
authors.lastname: Roboz
authors.forename: Peter
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authors.lastname: Maslak
authors.forename: Dan
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authors.lastname: Douer
authors.forename: Mark G
authors.initials: MG
authors.lastname: Frattini
authors.forename: Sergio
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authors.lastname: Giralt
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authors.lastname: Sadelain
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authors.lastname: Brentjens
mesh_terms: D000293:Adolescent; D000328:Adult; D017690:Cell Transplantation; D005260:Female; D006801:Humans; D007167:Immunotherapy; D015448:Leukemia, B-Cell / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult