Immunopharmacologic response of patients with B-lineage acute lymphoblastic leukemia to continuous infusion of T cell-engaging CD19/CD3-bispecific BiTE antibody blinatumomab

Blood. 2012 Jun 28;119(26):6226-33. doi: 10.1182/blood-2012-01-400515. Epub 2012 May 16.


T cell-engaging CD19/CD3-bispecific BiTE Ab blinatumomab has shown an 80% complete molecular response rate and prolonged leukemia-free survival in patients with minimal residual B-lineage acute lymphoblastic leukemia (MRD(+) B-ALL). Here, we report that lymphocytes in all patients of a phase 2 study responded to continuous infusion of blinatumomab in a strikingly similar fashion. After start of infusion, B-cell counts dropped to < 1 B cell/μL within an average of 2 days and remained essentially undetectable for the entire treatment period. By contrast, T-cell counts in all patients declined to a nadir within < 1 day and recovered to baseline within a few days. T cells then expanded and on average more than doubled over baseline within 2-3 weeks under continued infusion of blinatumomab. A significant percentage of reappearing CD8(+) and CD4(+) T cells newly expressed activation marker CD69. Shortly after start of infusion, a transient release of cytokines dominated by IL-10, IL-6, and IFN-γ was observed, which no longer occurred on start of a second treatment cycle. The response of lymphocytes in leukemic patients to continuous infusion of blinatumomab helps to better understand the mode of action of this and other globally T cell-engaging Abs. The trial is registered with identifier NCT00560794.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Antibodies, Bispecific / administration & dosage*
  • Antibodies, Bispecific / adverse effects
  • Antibodies, Bispecific / pharmacokinetics
  • Antigens, CD19 / immunology*
  • Antilymphocyte Serum / administration & dosage
  • Antilymphocyte Serum / adverse effects
  • Antilymphocyte Serum / metabolism
  • CD3 Complex / immunology*
  • Cytotoxicity, Immunologic / drug effects
  • Humans
  • Immune System / drug effects*
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / adverse effects
  • Immunologic Factors / pharmacokinetics
  • Immunotherapy / adverse effects
  • Immunotherapy / methods
  • Infusion Pumps
  • Lymphocyte Activation / drug effects
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Treatment Outcome


  • Antibodies, Bispecific
  • Antigens, CD19
  • Antilymphocyte Serum
  • CD3 Complex
  • Immunologic Factors
  • blinatumomab

Associated data