Rituximab is a chimeric monoclonal antibody that was developed for the treatment of B cell lymphomas.¹ It is directed against the CD20 cell surface molecule.² CD20 is a tetraspan membrane protein that is present only on B cells, and is expressed initially at the immature B cell stage, remaining until the final differentiation into plasma cells. The function of CD20 is not clear, although it may play some role in signalling or in calcium mobilisation.³ Curiously, mice that were genetically engineered to lack CD20 (CD20 knockout mice) have not shown any clear defects in their B cells.⁴ Nevertheless, the specificity of CD20 for the B cell lineage, and its failure to be easily shed or internalised, has made it an excellent target for depletion by monoclonal antibodies. Not only does rituximab kill CD20+ lymphoma cells, but it also substantially depletes normal B cells from the peripheral blood.⁵ Tissue depletion also occurs, but is perhaps less profound, and in any case has been little documented in patients.⁶ The mechanism of B cell depletion appears to be a combination of FcRγ dependent ADCC (antibody dependent cell mediated cytotoxocity), complement mediated lysis, and apoptosis,⁷ although the relative contributions of these mechanisms in vivo remains to be determined, In addition, stimulation of the inhibitory FcRγIIB may also play a role in rituximab therapeutic effects.⁸

CLINICAL DATA

In 1997, the US Food and Drug Administration (FDA) approved rituximab for the treatment of low grade non-Hodgkin’s B cell lymphomas.⁹ Since that time, it has been used in over 500 000 patients with generally excellent tolerability. Largely through a series of investigator sponsored trials supported in part by Genentech (South San Francisco, CA), the use of rituximab has been extended to a much wider spectrum of B cell malignancies, and strikingly, …