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

Craig A Portell, Candice M Wenzell, Anjali S Advani Leukemia 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,...

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Autores principales: Portell CA, Wenzell CM, Advani AS
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2013
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Acceso en línea:https://doaj.org/article/22d8a228028f4c9eb7976618ce4b5032
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Sumario:Craig A Portell, Candice M Wenzell, Anjali S Advani Leukemia 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: blinatumomab, B-cell acute lymphoblastic leukemia, CD19, BiTE antibodies