Frequency of regulatory T cells determines the outcome of the T-cell-engaging antibody blinatumomab in patients with B-precursor ALL

Leukemia. 2017 Oct;31(10):2181-2190. doi: 10.1038/leu.2017.41. Epub 2017 Jan 25.


Blinatumomab can induce a complete haematological remission in patients in 46.6% with relapsed/refractory B-precursor acute lymphoblastic leukemia (r/r ALL) resulting in a survival benefit when compared with chemotherapy. Only bone marrow blast counts before therapy have shown a weak prediction of response. Here we investigated the role of regulatory T cells (Tregs), measured by CD4/CD25/FOXP3 expression, in predicting the outcome of immunotherapy with the CD19-directed bispecific T-cell engager construct blinatumomab. Blinatumomab responders (n=22) had an average of 4.82% Tregs (confidence interval (CI): 1.79-8.34%) in the peripheral blood, whereas non-responders (n=20) demonstrated 10.25% Tregs (CI: 3.36-65.9%). All other tested markers showed either no prediction value or an inferior prediction level including blast BM counts and the classical enzyme marker lactate dehydrogenase. With a cutoff of 8.525%, Treg enumeration can identify 100% of all blinatumomab responders and exclude 70% of the non-responders. The effect is facilitated by blinatumomab-activated Tregs, leading to interleukin-10 production, resulting in suppression of T-cell proliferation and reduced CD8-mediated lysis of ALL cells. Proliferation of patients' T cells can be restored by upfront removal of Tregs. Thus, enumeration of Treg identifies r/r ALL patients with a high response rate to blinatumomab. Therapeutic removal of Tregs may convert blinatumomab non-responders to responders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Bispecific / immunology
  • Antibodies, Bispecific / therapeutic use*
  • Antigens, Differentiation, T-Lymphocyte / analysis
  • Cell Line, Tumor
  • Clinical Trials as Topic
  • Cytotoxicity, Immunologic
  • Female
  • Humans
  • Immunophenotyping
  • Immunotherapy*
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / genetics
  • Lymphocyte Activation
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Prognosis
  • Remission Induction
  • Salvage Therapy*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • Treatment Outcome


  • Antibodies, Bispecific
  • Antigens, Differentiation, T-Lymphocyte
  • IL10 protein, human
  • Interleukin-10
  • blinatumomab