Expert opinion on biological therapy · 2010
Ofatumumab, a human anti-CD20 monoclonal antibody.
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Osterborg Anders
Аннотация
IMPORTANCE OF THE FIELD: Since relapse of chronic lymphocytic leukemia (CLL), and refractoriness to treatment following relapse, is inevitable after initial treatment, development of novel treatment strategies is necessary.
AREAS COVERED IN THIS REVIEW: CD20 as a therapeutic target for CLL, successes and limitations of current anti-CD20 monoclonal antibody (mAb) therapy, and implications of preclinical and clinical developments of novel alternatives, including ofatumumab, that may enhance anti-CD20 mAb therapy are reviewed. The literature reviewed encompasses papers and congress abstracts from the past 13 years.
WHAT THE READER WILL GAIN: While rituximab combined with chemotherapy has considerably improved outcomes for some but not all CLL patients, single-agent use is limited in relapsed/refractory CLL. Novel anti-CD20 mAbs in development, such as ofatumumab, may bypass some limitations by virtue of alternative epitope binding and modified effector functions. Ofatumumab induces significant complement-dependent cell lysis in vitro, particularly in cells with low CD20 expression. The FDA recently approved ofatumumab for treatment of CLL refractory to fludarabine and alemtuzumab.
TAKE HOME MESSAGE: CD20-targetting chemoimmunotherapeutic options have advanced treatment of CLL. Results for single-agent ofatumumab and other new CD20 mAbs, in different lines of therapy and in combination with chemotherapy, will guide optimal use of these alternative therapies for B-cell malignancies.
AREAS COVERED IN THIS REVIEW: CD20 as a therapeutic target for CLL, successes and limitations of current anti-CD20 monoclonal antibody (mAb) therapy, and implications of preclinical and clinical developments of novel alternatives, including ofatumumab, that may enhance anti-CD20 mAb therapy are reviewed. The literature reviewed encompasses papers and congress abstracts from the past 13 years.
WHAT THE READER WILL GAIN: While rituximab combined with chemotherapy has considerably improved outcomes for some but not all CLL patients, single-agent use is limited in relapsed/refractory CLL. Novel anti-CD20 mAbs in development, such as ofatumumab, may bypass some limitations by virtue of alternative epitope binding and modified effector functions. Ofatumumab induces significant complement-dependent cell lysis in vitro, particularly in cells with low CD20 expression. The FDA recently approved ofatumumab for treatment of CLL refractory to fludarabine and alemtuzumab.
TAKE HOME MESSAGE: CD20-targetting chemoimmunotherapeutic options have advanced treatment of CLL. Results for single-agent ofatumumab and other new CD20 mAbs, in different lines of therapy and in combination with chemotherapy, will guide optimal use of these alternative therapies for B-cell malignancies.