Clinical applications and safety evaluation of the new CD19 specific T-cell engager antibody construct blinatumomab

Expert Opin Drug Saf. 2017 Oct;16(10):1191-1202. doi: 10.1080/14740338.2017.1338270. Epub 2017 Aug 20.

Abstract

Blinatumomab is a T-cell engager antibody construct with dual specificity for CD19 and CD3, inducing serial lysis of CD19 positive B cells by redirecting cytotoxic T cells. It has been approved for the indication of Ph chromosome negative relapsed or refractory B-acute lymphoblastic leukemia (ALL), but has also been tested in ALL with minimal residual disease, relapsed Ph/BCR-ABL positive ALL, relapsed ALL in pediatric patients and relapsed or refractory non-Hodgkin's lymphoma (NHL). Adverse events have been mainly related to infection and hematological toxicities, as well as cytokine release syndrome and neurotoxicity. Areas covered: The review will discuss mechanisms of action, published literature on efficacy in ALL and NHL, specific aspects of administration, frequent adverse events and practical management. Expert opinion: Blinatumomab represents an effective new treatment for highly resistant relapsed/refractory B-precursor ALL. Practical handling bears challenges due to application as four week continous infusion and specific adverse effects which can be well handled by experienced centers. Most promising outcomes are reported for patients with resistant disease but lower tumor load such as MRD positive ALL patients. Future studies will focus on the use of blinatumomab during first-line therapy and the role of stem cell transplantation after blinatumomab treatment.

Keywords: Acute lymphoblastic leukemia; CD19; antibody; immunotherapy; minimal residual disease; relapse.

Publication types

  • Review

MeSH terms

  • Antibodies, Bispecific / administration & dosage*
  • Antibodies, Bispecific / adverse effects
  • Antigens, CD19 / immunology
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Humans
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Lymphoma, Non-Hodgkin / immunology
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology

Substances

  • Antibodies, Bispecific
  • Antigens, CD19
  • Antineoplastic Agents
  • blinatumomab