Rituximab for the treatment of diffuse large B-cell lymphomas

Abstract

For more than 25 years, the combination of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) was considered the gold standard for the treatment of aggressive lymphomas, 90% of which are diffuse, large B-cell lymphomas (DLBCLs). Attempts to improve results by more intensive chemotherapy regimens, including high-dose chemotherapy approaches necessitating stem-cell support, have not convincingly shown improved outcome of DLBCL. The chimeric monoclonal antibody rituximab, which binds to the CD20 antigen expressed on normal B cells and the malignant cells of more than 90% of DLBCLs, and mediates lysis of these cells by direct induction of apoptosis, activation of complement- and antibody-dependent cellular cytotoxicity in vitro, is an attractive candidate for the treatment of B-cell lymphomas. Initial studies in follicular lymphoma demonstrated its efficacy as a single agent or in combination with chemotherapy without adding relevant toxicity. After the demonstration of rituximab single-agent activity in DLBCL, a pivotal trial in elderly patients demonstrated that combining rituximab with eight applications of CHOP significantly improved complete remission, event-free and overall survival rates when compared with CHOP alone. These positive results have meanwhile been confirmed by two additional randomized trials in elderly patients and have been extended to young patients with good-prognosis DLBCL by a fourth trial. While not yet formally established in young, poor-prognosis patients, rituximab in combination with CHOP has become accepted worldwide as the new standard for the treatment of DLBCL. Questions remain concerning the optimal dosage and schedule of rituximab for DLBCL, as well as the optimal chemotherapy regimen partner for rituximab. Rituximab is the first monoclonal antibody to consistently improve survival rates of patients with a malignant disease. Its excellent efficacy in combination with cytotoxic chemotherapy, together with its favorable toxicity profile, establishes rituximab as an indispensable component of modern standard immunochemotherapy of DLBCL.