title: Clinical and pharmacologic aspects of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia.
abstract: Acute lymphoblastic leukemia (ALL) in adults remains a challenging disease to treat, and novel therapies are needed. Precursor-B ALL comprises 80% of cases, and the CD19 antigen is expressed in nearly all precursor-B ALL patients. Bispecific T-cell-engaging antibodies are novel bioengineered proteins. The bispecific T-cell-engaging antibody blinatumomab engages polyclonal T cells to CD19-expressing B cells. By binding to both CD3 and CD19, blinatumomab physically brings these T cells in close proximity to malignant B cells and potentiates T-cell-induced cytotoxic cell kill. Blinatumomab requires continuous intravenous infusion due to its short half-life, the need for continuous exposure for the drug to exert sufficient efficacy, and lessened toxicity. A phase II trial of B-cell ALL patients with persistent or relapsed minimal residual disease demonstrated an 80% rate of complete molecular remission. Cytokine-release syndrome and central nervous system events, such as seizures and encephalopathy, are reversible toxicities. Promising results in B-cell ALL with minimal residual disease have led to further evaluation of this drug in newly diagnosed and relapsed B-cell ALL.
authors.affiliation: Leukemia Program, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Portell
authors.forename: Candice M
authors.initials: CM
authors.lastname: Wenzell
authors.forename: Anjali S
authors.initials: AS
authors.lastname: Advani
keywords: B-cell acute lymphoblastic leukemia; BiTE antibodies; CD19; blinatumomab