Optimizing the use of rituximab for treatment of B-cell non-Hodgkin's lymphoma: a benefit-risk update.

Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA and IDEC Pharmaceutical Corporation, San Diego, CA), the first monoclonal antibody approved in the United States for the treatment of cancer, is indicated for the treatment of patients with relapsed or refractory CD20+ low-grade non-Hodgkin's lymphoma. From November 1997 through May 1999, approximately 36,000 patients have been treated with rituximab. Serious cardiopulmonary infusion reactions culminating in death have been reported to occur in approximately 0.04% to 0.07% of patients. Post-approval tumor lysis syndrome has been reported within 12 to 24 hours after the first antibody infusion and is estimated to occur in 0.04% to 0.05% of patients. The risk of tumor lysis appears to be higher in patients with high numbers of circulating malignant cells. Serious infusion-related adverse drug reactions, most often consisting of cardiopulmonary reactions associated with the rapid lysis of large numbers of circulating malignant cells, have been fatal in approximately 0.5 per 1,000 treated patients. Major risk factors include high numbers of circulating malignant lymphoma cells, pulmonary infiltrates or lymphoma involvement, and prior cardiovascular disease. This report updates the safety experience of rituximab therapy with data from clinical trials and postmarketing safety experience, and examines how this information can be used to optimize therapy.