Treatment of low-grade B-cell lymphoma with the monoclonal antibody rituximab

The anti-CD20 chimeric monoclonal antibody has been a tremendous addition to the therapeutic armamentarium against low-grade lymphoma. In indolent lymphoma, rituximab as a single agent is associated with 50% to 60% objective response rates in the relapsed setting and 60% to 75% as front-line therapy. Chemotherapy plus rituximab combinations have been associated with response rates of 85% to 95% and randomized trials have confirmed a higher response rate for various chemotherapy plus rituximab combinations compared to the same chemotherapy alone. Concurrent chemotherapy with rituximab does not increase toxicity and appears superior to sequences of chemotherapy followed by rituximab. Repeated intermittent therapy is associated with higher response rates and longer duration of remission. When used alone, the activity of rituximab is probably due to a combination of complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and regulatory effects that enhance apoptosis. Dosing could probably be optimized by monitoring serum levels of rituximab in individual patients, because of the tremendous variability in lymphoma tumor burden, rates of tumor proliferation, rates of CD20 antigen production and expression, and clearance of rituximab. Combinations of rituximab with other monoclonal antibodies are currently being tested.