Obinutuzumab is a novel therapeutic anti-CD20
monoclonal antibody recently approved by the United States Food and Drug Administration (FDA) for use in combination with
chlorambucil as first-line treatment of
chronic lymphocytic leukemia (CLL). It is distinguished from other anti-B-lymphocyte
antigen CD20 (anti-CD20) therapeutic
antibodies in current clinical use by its type II properties and glycoengineered Fc region. In vitro these unique properties translate into higher rates of antibody-dependent cytotoxicity and direct cell death compared to
rituximab, and
obinutuzumab demonstrates improved efficacy in human
lymphoma xenograft models and whole blood lymphocyte depletion assays. FDA approval was based upon results from a randomized phase III trial comparing treatment with single-agent
chlorambucil to the combination of
chlorambucil and either
rituximab or obinutuzu-mab. The
obinutuzumab arm resulted in higher rates of complete remission and significant improvements in progression-free survival versus either comparator regimen. The majority of patients in the
obinutuzumab and
chlorambucil arm finished all six planned treatment cycles, and
therapy was well tolerated. Toxicities of
obinutuzumab are similar to those of other anti-CD20
antibodies, although infusion-related reactions and
neutropenia appear to be more common. This trial establishes chemoimmunotherapy with
obinutuzumab and
chlorambucil as an attractive treatment option for CLL patients, particularly those with comorbid medical illnesses or advanced age.
Obinutuzumab remains under study in combination with both
chemotherapy and novel agents for CLL and
non-Hodgkin's lymphoma, where it is expected to find additional clinical applications.