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Clin Pharmacol. 2013 Apr 12;5(Suppl 1):5-11. doi: 10.2147/CPAA.S42689. Print 2013.

Clinical and pharmacologic aspects of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia.

Author information

  • 1Leukemia Program, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.

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.

KEYWORDS:

B-cell acute lymphoblastic leukemia; BiTE antibodies; CD19; blinatumomab

PMID:
23671399
PMCID:
PMC3650887
DOI:
10.2147/CPAA.S42689
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