What is the status of novel anti-CD20 antibodies for chronic lymphocytic leukemia and are they set to leave rituximab in the shadows?

Abstract

Chronic lymphocytic leukemia/small lymphocytic lymphoma is the most prevalent form of adult leukemia in western countries. Chemotherapy has been the mainstay of treatment for the last several decades. The introduction of biological, targeted agents (e.g., monoclonal antibodies) has dramatically improved treatment options. The addition of rituximab to fludarabine and cyclophosphamide has improved patient outcomes, as compared to fludarabine and cyclophosphamide. Nevertheless, chronic lymphocytic leukemia remains incurable, leaving considerable room for improvement. One approach would be to enhance the activity of the CD20 antibody. The next-generation monoclonal antibody ofatumumab has not demonstrated superiority over rituximab, whereas obinutuzumab–chlorambucil is superior to rituximab–chlorambucil. Recent efforts to combine anti-CD20 antibodies with new targeted therapies offer the potential to move toward alternative non-chemotherapy–based treatment approaches.

Keywords:

• anti-CD20 monoclonal antibody
• biologics
• biosimilars
• CD20 antigen
• chronic lymphocytic leukemia
• immunomodulatory agents
• indolent non-Hodgkin’s lymphoma
• small molecule kinase inhibitors

Financial & competing interests disclosure

The study was supported by the Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital. B Cheson is a consultant to Roche-Genentech with research funding to the institution. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• The current focus in the treatment of chronic lymphocytic leukemia is biologic targeted therapies.

• Next-generation monoclonal antibodies targeting CD20 have shown some activity in rituximab-refractory patients, but have not yet shown superiority over rituximab.

• Small molecule kinase inhibitors target the various intracellular pathways downstream to the B-cell receptor in malignant B cells.

• Current research efforts are looking at combinations of these targeted agents for dual pathway inhibition with the goal to improve the quality and durability of response and eventually cure chronic lymphocytic leukemia.

Notes