Alemtuzumab (Campath-1H) in the treatment of chronic lymphocytic leukemia

Abstract

Alemtuzumab (Campath-1H) is a humanized IgG1 monoclonal antibody that targets the human CD52 antigen. CD52 is expressed by a variety of lymphoid neoplasms and most human mononuclear cell subsets. In 2001, alemtuzumab was approved for marketing in the United States and Europe for use in patients with fludarabine-refractory chronic lymphocytic leukemia (CLL). In heavily pretreated patients with CLL, the overall response rate (ORR) is approximately 35%, and in previously untreated patients the ORR is greater than 80%, with a recent randomized study suggesting it is superior to alkylator-based therapy. Importantly, alemtuzumab is effective in patients with high-risk del(17p13.1) and del(11q22.3) CLL. Alemtuzumab combination studies with fludarabine and/or monoclonal antibodies such as rituximab have demonstrated promising results. Alemtuzumab is also being studied in CLL patients as consolidation therapy for treatment of minimal residual disease, in preparation for stem cell transplantation and to prevent acute and chronic graft versus host disease. Alemtuzumab is frequently associated with acute 'first-dose' reactions when administered intravenously, but is much better tolerated when administered subcutaneously without loss of therapeutic efficacy. Additional potential adverse events associated with alemtuzumab administration include myelosuppression as well as profound cellular immune dysfunction with the associated risk of viral reactivation and other opportunistic infections. Additional studies detailing the mechanism of action of alemtuzumab as well as new strategies for prevention of opportunistic infections will aid in the future therapeutic development of this agent.