title: Blinatumomab for the treatment of acute lymphoblastic leukemia.
abstract: BACKGROUND
  Acute lymphoblastic leukemia (ALL) is a potentially fatal disease that involves clonal expansion of early lymphoid progenitor cells. Much of drug development for ALL treatment involves targeting antigens of the clonal cell surface. Blinatumomab belongs to an emerging class of anti-cancer therapeutics referred to as bispecific T-cell engaging antibodies. The Food and Drug Administration approved its use in relapsed or refractory adult Philadelphia chromosome-negative B-cell precursor ALL in December of 2014.
  Blinatumomab contains both an anti-CD3 and anti-CD19 arm, allowing for the juxtaposition of CD3+ T-cells to malignant CD19+ B-cells, thereby resulting in granzyme- and perforin-mediated B-cell apoptosis.
  Preclinical studies suggest that blinatumomab's efficacy is related to the effector-to-target ratio and to the difference between its affinity for CD19 and CD3.
  Preclinical and early phase clinical studies have allowed for the characterization of the pharmacokinetics of blinatumomab, including the determination of its short half-life. The metabolic pathway has not been fully characterized but is thought to be similar to that of other antibodies.
  
  
  METHODS
  Phase I and II studies led to the identification of an ideal stepwise dose, involving long-term continuous intravenous infusion (CIVI), to optimize its efficacy and reduce the risk of certain toxicities. A high remission rate and duration were noted among a relapsed/refractory population of patients.
  
  
  RESULTS
  The results of clinical trials have identified cytokine release syndrome and neurotoxicity, among others, as serious drug-related toxicities, leading to the institution of a Risk Evaluation and Mitigation Strategy.
  
  
  CONCLUSIONS
  Blinatumomab represents a significant addition to the treatment options for ALL, but it is not without its limitations, of which are its short-half life, necessitating long-term CIVI, and the eventual emergence of CD19-negative clones. Continual development of the agent involves assessing its role in the frontline setting and in combination with chemotherapy.
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center of Northwestern University, 233 E. Superior St., First floor, Chicago, IL, 60611, USA. jason.kaplan@northwestern.edu.|Division of Hematology and Oncology and Northwestern Medicine Developmental Therapeutics Institute (NMDTI), Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. jason.kaplan@northwestern.edu.
authors.forename: Jason B
authors.initials: JB
authors.lastname: Kaplan
authors.affiliation: Division of Hematology and Oncology and Northwestern Medicine Developmental Therapeutics Institute (NMDTI), Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Grischenko
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center of Northwestern University, 233 E. Superior St., First floor, Chicago, IL, 60611, USA.|Division of Hematology and Oncology and Northwestern Medicine Developmental Therapeutics Institute (NMDTI), Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000379:methods; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology
chemical_list: D018033:Antibodies, Bispecific; D000970:Antineoplastic Agents; C510808:blinatumomab
keywords: Acute lymphoblastic leukemia; Bispecific T-cell engager; Blinatumomab; CD19; Targeted therapy