Targeted therapy with monoclonal antibodies in acute lymphoblastic leukemia

Abstract

Purpose of review: To describe the current new targeted therapy with monoclonal and bispecific antibodies in adult acute lymphoblastic leukemia (ALL), to improve response rates and outcome.

Recent findings: 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.

Summary: 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.