Emerging information on the use of rituximab in chronic lymphocytic leukemia.
Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC Pharmaceuticals, San Diego, CA) is a chimeric monoclonal antibody that targets mature B cells in most lymphoid B-cell malignancies. While rituximab was approved by the US Food and Drug Administration for the treatment of recurrent B-cell lymphoma, initial studies suggested that it had less activity in small lymphocytic lymphoma, the nodal counterpart of chronic lymphocytic leukemia (CLL). Two studies have now investigated the activity of higher-dose and more intensive therapy with rituximab in CLL. They have shown a dose-response relationship and a higher response rate than previously seen in the lower-dose studies. This is presumably caused by the overcoming of lower antigen density on CLL cells compared with lymphoma cells, and the shorter half-life of rituximab in small lymphocytic lymphoma. There is now evidence that CD20 is shed into the plasma in patients with CLL, which may explain the shorter half-life of the antibody in small lymphocytic lymphoma/CLL. The higher dose may then be effective in overcoming this so-called "antigen sink." Toxicity was uncommon except in previously untreated patients and those with atypical forms of CLL such as mantle cell lymphoma and prolymphocytic leukemia. There is now evidence in vitro of additive or synergistic activity of rituximab with a variety of chemotherapeutic agents including fludarabine and cyclophosphamide. Combinations of fludarabine with rituximab or these two drugs combined with cyclophosphamide have given very high complete response rates in series of patients with both previously untreated and treated CLL. It is apparent that rituximab is playing a significant role in the management of patients with CLL as salvage therapy and is a potential potentiating agent for combined chemoimmunotherapy strategies for front-line or relapsed patients with CLL.
Keating
Michael J
MJ
Leukemia Department, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
O'Brien
Susan
S
Albitar
Maher
M
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003520:Cyclophosphamide / Q000008:administration & dosage; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D000069283:Rituximab; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine