The Monoclonal Antibodies Campath-1H and Rituximab in theTherapy of Chronic Lymphocytic Leukemia.
The treatment options for chronic lymphocytic leukemia (CLL) beside standard therapy with chlorambucil or other alkylating agents have dramatically increased in the last few years. Promising results have been reported with new cytotoxic agents such as the purine analogues fludarabine and 2-chlordeoxyadenosine, either at first diagnosis or at relapse. Nevertheless, all patients with CLL relapse after initial response. Since residual lymphoma cells are very likely to be the origin of the clinical relapse, there is a need for new therapeutic approaches with different mechanism of action to eliminate these residual cells. These approaches include allogeneic or autologous stem cell transplantation as well as immunotherapeutic strategies. Monoclonal antibodies, either alone or conjugated to toxins or radioisotopes, are thus being actively investigated. In clinical trials the genetically engineered chimeric unconjugated anti-CD20 antibody Rituximab and the humanized unconjugated anti-CD52 antibody Campath-1H achieved the most promising results in the treatment of patients with relapsed or refractory low-grade non-Hodgkin's lymphoma. Thus far there is only little clinical experience with Rituximab in patients with CLL, and the exact role of these agent in the treatment of CLL has still to be determined in ongoing and future trials. As a single agent Campath-1H showed more clinical activity in previously treated CLL patients than Rituximab, with response rates of up to 33% in a multicenter pivotal study. Furthermore, the potential risks of tumor lysis and anaphylaxia for both antibodies and immunosuppression particularly for Campath-1H must be taken into account. The present review will compare the development and the basic principles of these unconjugated monoclonal antibodies and consider their present and potential role in the treatment of patients with CLL. Copyright 2000 S. Karger GmbH, Freiburg
Schulz
H.
H
Klinik I für Innere Medizin, Universität zu Köln.
Winkler
U.
U
Staak
J.O.
JO
Engert
A.
A