title: Blinatumomab: A First-in-Class Bispecific T-Cell Engager for Precursor B-Cell Acute Lymphoblastic Leukemia.
abstract: OBJECTIVE
  To review the clinical pharmacology, efficacy, and safety of blinatumomab for the treatment of pediatric and adult precursor B-cell acute lymphoblastic leukemia (B-ALL).
  
  
  METHODS
  A literature search of EMBASE (1947 to April 2015), Medline (1946 to April 2015), PubMed (1996 to April 2015), the U.S. National Institutes of Health Clinicaltrials.gov, the Food and Drug Administration, and relevant meeting abstracts was conducted using the terms blinatumomab, BiTE, bispecific T-cell engager, MT103, MEDI-538, and Blincyto.
  
  
  METHODS
  Human and animal studies describing the pharmacology, pharmacokinetics and pharmacodynamics, efficacy, and safety of blinatumomab for precursor B-ALL were identified.
  
  
  RESULTS
  Blinatumomab is a first-in-class bispecific T-cell engager (BiTE) antibody derived from a B-lineage specific antitumor mouse monoclonal antibody that binds to both CD19 of B-cells and CD3 of T-cells. A pivotal phase II trial demonstrated that response rates were high in a refractory or relapsed patient population, with 43% achieving complete remission (CR). Median relapse-free survival was 5.9 months for those with CR or CR with incomplete hematological recovery. Median overall survival was 6.1 months, and 60% of patients achieved minimal residual disease (MRD) negativity. The most common adverse events included pyrexia, neurological events, headache, febrile neutropenia, peripheral edema, nausea, hypokalemia, constipation, and anemia.
  
  
  CONCLUSIONS
  Blinatumomab is a novel BiTE therapeutic monoclonal antibody that has shown promising results in patients with relapsed or refractory ALL or those achieving a CR with persistent MRD. Phase III clinical trials should define the optimal place in therapy of blinatumomab.
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA buiel@mskcc.org.
authors.forename: Larry W
authors.initials: LW
authors.lastname: Buie
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Pecoraro
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Troy Z
authors.initials: TZ
authors.lastname: Horvat
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Daley
mesh_terms: D000208:Acute Disease; D000818:Animals; D018033:Antibodies, Bispecific / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004347:Drug Interactions; D006801:Humans; D051379:Mice; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000276:immunology; D012074:Remission Induction; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018033:Antibodies, Bispecific; D000970:Antineoplastic Agents; C510808:blinatumomab
keywords: B-cell acute lymphoblastic leukemia; BiTE; Blincyto; blinatumomab