Targeted therapy with monoclonal antibodies in acute lymphoblastic leukemia

Abstract

To describe the current new targeted therapy with monoclonal and bispecific antibodies in adult acute lymphoblastic leukemia (ALL), to improve response rates and outcome. Blast cells in ALL express a variety of specific antigens, such as CD19, CD20, CD22, CD33 and CD52, and recently monoclonal antibodies (MoAbs) became available to target these antigens. The anti-CD20 MoAb rituximab has substantially improved the outcome in Burkitt lymphoma/leukemia, and is currently applied in de-novo B-precursor ALL. The MoAbs directed against CD22, linked to cytotoxic agents, either to calicheamicin (inotuzomab ozogamicin) or to plant or bacterial toxins (epratuzumab) are explored in refractory/relapsed childhood and adult ALL. Targeting CD19 is of great interest, as it is expressed in all B-lineage cells, including early precursors. The new bispecific antibody blinatumomab combines single chain antibodies to CD19 and CD3, and thereby T cells lyse the CD19 bearing B cells and is effective in patients with positive minimal residual disease (MRD) or refractory/relapsed ALL. Antibody therapy in ALL is very promising, with high rate of complete remission and MRD-negativity in advanced ALL. It is currently explored in de-novo ALL to establish the best setting in combination with chemotherapy or even as a monotherapy.