Clinical review: Serious adverse events associated with the use of rituximab - a critical care perspective

Abstract

The advent of biologic agents has provided a more specific and targeted approach to the treatment of various hematological malignancies and other autoimmune disorders. Such biologic agents have been relatively well tolerated with fewer adverse events reported as compared with many other chemotherapeutic agents. Rituximab is a monoclonal antibody to the B-cell marker CD20 and is a common biologic agent widely used for the treatment of B-cell lymphoma, lymphoproliferative disorders, and inflammatory conditions that are refractory to conventional treatment, including rheumatoid arthritis and some vasculitides. However, through randomized controlled trials and post-marketing surveillance, an increasing number of serious adverse events are being associated with the use of rituximab, often leading to or complicating an intensive care unit admission. The purpose of this review is to focus on the severe complications that are associated with the use of rituximab and that require critical care. Management and prevention strategies for the most common complications along with some examples of its uses within the critical care setting are also discussed.

Figure 1

The proposed mechanisms of action for rituximab, a chimeric monoclonal antibody, against the CD 20 receptor. (1) Antibody-dependent cell-mediated cytotoxicity (ADCC). Effector cells include natural killer cells and phagocytic cells such as monocytes and macrophages that express Fc receptors. (2) Complement-dependent cytotoxicity (CDC). (3) Direct effects of binding (induction of apoptosis and sensitization to other chemotherapeutic agents). (4) Antibody-dependent phagocytosis (ADP).

Figure 2

Major serious adverse events as categorized by the system organ class devised by the National Cancer Institute.