Antigen-based immunotherapy for the treatment of acute lymphoblastic leukemia: the emerging role of blinatumomab

Abstract

Acute lymphoblastic leukemia (ALL) arises from immature B and T lymphoblasts. An increasing array of cytogenetic and molecular markers have been identified in ALL, which allows for increasingly sophisticated prognostication, as well as identification of potential new targets for therapy. The treatment of ALL in children has shown astounding success in the last 50 years, with more than 90% of children now able to be cured of their ALL. In adults, these success rates have not been duplicated. However, the use of pediatric-intensive regimens in young adults has shown increasing success. The use of monoclonal antibodies conjugated to drugs, immunotoxins, and cells also has shown early success and promises to enhance the outcome of newly diagnosed patients. Blinatumomab, a bispecific T-cell engager antibody, brings a malignant B cell in proximity to a T cell with redirected lysis. This antibody construct has shown promising results in patients with relapsed and refractory disease and is entering randomized clinical trials in newly diagnosed patients. The addition of monoclonal antibody therapy to chemotherapy in adults promises to enhance outcomes while hopefully not increasing toxicity. After many years of stagnation, it appears that the therapy of adults with ALL is showing significant improvement.