Toxicity and response after CD19-specific CAR T-cell therapy in pediatric/young adult relapsed/refractory B-ALL

Blood. 2019 Dec 26;134(26):2361-2368. doi: 10.1182/blood.2019001641.

Abstract

Chimeric antigen receptor (CAR) T cells have demonstrated clinical benefit in patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We undertook a multicenter clinical trial to determine toxicity, feasibility, and response for this therapy. A total of 25 pediatric/young adult patients (age, 1-22.5 years) with R/R B-ALL were treated with 19-28z CAR T cells. Conditioning chemotherapy included high-dose (3 g/m2) cyclophosphamide (HD-Cy) for 17 patients and low-dose (≤1.5 g/m2) cyclophosphamide (LD-Cy) for 8 patients. Fifteen patients had pretreatment minimal residual disease (MRD; <5% blasts in bone marrow), and 10 patients had pretreatment morphologic evidence of disease (≥5% blasts in bone marrow). All toxicities were reversible, including severe cytokine release syndrome in 16% (4 of 25) and severe neurotoxicity in 28% (7 of 25) of patients. Treated patients were assessed for response, and, among the evaluable patients (n = 24), response and peak CAR T-cell expansion were superior in the HD-Cy/MRD cohorts, as compared with the LD-Cy/morphologic cohorts without an increase in toxicity. Our data support the safety of CD19-specific CAR T-cell therapy for R/R B-ALL. Our data also suggest that dose intensity of conditioning chemotherapy and minimal pretreatment disease burden have a positive impact on response without a negative effect on toxicity. This trial was registered at www.clinicaltrials.gov as #NCT01860937.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antigens, CD19 / metabolism*
  • Child
  • Child, Preschool
  • Cytokine Release Syndrome / etiology
  • Cytokine Release Syndrome / pathology
  • Cytokine Release Syndrome / prevention & control
  • Drug Resistance, Neoplasm*
  • Female
  • Humans
  • Infant
  • Male
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / therapy*
  • Neoplasm, Residual / etiology
  • Neoplasm, Residual / pathology
  • Neoplasm, Residual / prevention & control
  • Neurotoxicity Syndromes / etiology
  • Neurotoxicity Syndromes / pathology
  • Neurotoxicity Syndromes / prevention & control
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Chimeric Antigen / immunology*
  • Salvage Therapy
  • Survival Rate
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation*
  • Treatment Outcome
  • Young Adult

Substances

  • Antigens, CD19
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen

Associated data

  • ClinicalTrials.gov/NCT01860937