Rituximab is a chimeric anti-CD20 mAb (Figure 33.1), containing the mouse variable domains of the mAb 2B8 grafted to the human IgG1 constant domains. Rituximab kills CD20+ cells by several mechanisms, including (1) complement-dependent cellular cytotox-icity, (2) antibody-dependent cellular cytotoxicity, and (3) induction of apoptosis.32 Both early phase II testing and phase II pivotal testing of rituximab at 375 mg/m2 per week X 4 in relapsed low-grade NHL demonstrated overall response rates of up to 48% (6% CR). The majority of toxic events were infusion related (hypotension, bronchospasm, rhinitis, pruritis, rash, urticaria, and tumor pain) and decreased with repeated dosing. Human antimouse antibodies (HAMA) were not observed. This led to Food and Drug Administration's approval of rituximab for indolent NHL. Its effect against indolent NHL was greatly enhanced by combining the drug with chemotherapy, with 95% overall response rates and 55% CR in patients receiving CHOP [cyclophosphamide, hydroxydaunomycin (doxorubicin), Oncovin (vincristine), and prednisone] plus rituximab.33 Activity with or without chemotherapy was reported in other B-cell malignancies, including aggressive NHL, mantle cell lymphoma, CLL, and Waldenstrom's macroglobulinemia.34-36
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