The future of CD20 monoclonal antibody therapy in B-cell malignancies

Leuk Lymphoma. 2010 Jun;51(6):983-94. doi: 10.3109/10428191003717746.

Abstract

Limitations of therapeutic options for chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) have necessitated the development of novel treatments/strategies. Rituximab (chimeric anti-CD20 monoclonal antibody [mAb]) considerably improved therapeutic outcomes for patients with B-cell malignancies, particularly when combined with chemotherapy; outcomes, however, are limited by rituximab resistance or reduced response upon re-treatment. Novel anti-CD20 mAbs are in development that may enhance mAb therapy. Ofatumumab (human anti-CD20 mAb) induces highly potent cell lysis, including in cells with low CD20 expression, and is the most clinically advanced new anti-CD20 mAb. Positive phase III interim data for ofatumumab in fludarabine-refractory CLL that is also refractory to alemtuzumab or less suitable for alemtuzumab due to bulky (>5 cm) lymphadenopathy has led to FDA approval of this agent in this population. Preclinical and early clinical assessment of other novel anti-CD20 mAbs include: ocrelizumab, veltuzumab, GA101, AME-133v, and PRO131921; data suggest potential for improved efficacy over rituximab that will require substantiation in large-scale clinical trials. New treatment strategies and novel anti-CD20 mAbs have the potential to enhance long-term outcomes for CLL and NHL.

Publication types

  • Review

MeSH terms

  • Alemtuzumab
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal, Murine-Derived
  • Antibodies, Neoplasm / immunology
  • Antibodies, Neoplasm / therapeutic use
  • Antigens, CD20 / immunology*
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / pathology
  • Clinical Trials as Topic
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Rituximab

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal, Murine-Derived
  • Antibodies, Neoplasm
  • Antigens, CD20
  • Alemtuzumab
  • Rituximab
  • ofatumumab