4. Antibody therapy for malignant lymphoma.

Rituximab, a genetically engineered, chimeric anti-CD20 monoclonal antibody, induces the apoptosis of B-lymphoma cells, in addition to the lyses by complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC), as shown in Fig. 1. A Japanese phase I study of rituximab in relapsed or refractory patients with B-cell non-Hodgkin's lymphoma (B-NHL) showed an overall response rate (ORR) of 64% (7/11) with minimal toxicities. Elimination half-life (T(1/2)) of serum rituximab was 445+/-361 hours, and the serum rituximab was detectable at three months. In the subsequent phase II study, 90 relapsed or refractory patients with indolent B-NHL or mantle cell lymphoma (MCL) were treated with rituximab at 375 mg/m2x4 weekly infusions. ORRs in indolent B-NHL and MCL were 61% (37/61) and 46% (6/13), respectively. In this presentation, the results of clinical trials of antibody therapy of malignant lymphoma are summarized, focusing on the two recent Japanese multicenter trials of rituximab and a Japanese feasibility study of anti-CD20 radioimmunotherapy with yttrium-90-lableled ibritumomab tiuxetan.