Bispecific antibodies in acute lymphoblastic leukemia therapy

Expert Rev Hematol. 2020 Nov;13(11):1211-1233. doi: 10.1080/17474086.2020.1831380. Epub 2020 Nov 4.


Introduction: Blinatumomab, first in a class of bispecific T-cell engagers, revolutionized treatment paradigm of B-cell precursor relapsed/refractory or minimal residual disease positive acute lymphoblastic leukemia (ALL) in adults and children, inducing deep remissions in a proportion of patients. However, significant numbers of patients do not respond or eventually relapse. Strategies for improvement of treatment outcomes are required.

Areas covered: This review discusses the main structural and functional features of blinatumomab, and its place in the treatment of ALL. Furthermore, prospects to increase the efficacy of blinatumomab are addressed. The developments in the field of bispecific antibodies and their possible implications for treatment of ALL are reviewed.

Expert opinion: Better understanding the mechanisms of response and resistance to blinatumomab might help us to identify the group of patients benefiting most from treatment and to spare potentially toxic subsequent treatment strategies. Data emerging from ongoing clinical trials might change the treatment landscape of ALL and beyond. Early use of blinatumomab in frontline protocols with more advantageous treatment sequences and in combination with other targeted therapies might reduce the failure rates. Exponentially increasing number of novel treatment options and their possible combinations might complicate treatment decision-making without data from randomized trials.

Keywords: Acute lymphoblastic leukemia; T cells; T-cell engagers; bispecific antibodies; blinatumomab; cytokine release syndrome; immunotherapy; neurotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Bispecific / adverse effects
  • Antibodies, Bispecific / economics
  • Antibodies, Bispecific / immunology
  • Antibodies, Bispecific / pharmacokinetics
  • Antibodies, Bispecific / therapeutic use*
  • Antigens, CD / analysis
  • Antigens, Neoplasm / analysis
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Child
  • Clinical Trials as Topic
  • Combined Modality Therapy
  • Drug Resistance, Neoplasm
  • Forecasting
  • Humans
  • Immunotherapy / methods*
  • Immunotherapy, Adoptive
  • Neoplasm, Residual
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Prognosis
  • Recurrence
  • Remission Induction
  • Salvage Therapy
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology


  • Antibodies, Bispecific
  • Antigens, CD
  • Antigens, Neoplasm
  • Antineoplastic Agents, Immunological
  • blinatumomab