Minimal residual disease elimination by consolidation therapy with alemtuzumab

Chronic lymphocytic leukemia (CLL) is one of the most common hematologic malignancies in the developed world. In recent decades, the development of novel therapies has greatly expanded the range of treatment options, including monoclonal antibodies. New methods for detecting residual disease have also been developed and are being used to assess the depth of clinical response achieved with novel treatment strategies. One such strategy involves the use of the monoclonal antibody as consolidation therapy to eradicate minimal residual disease (MRD) following chemotherapeutic induction. Alemtuzumab is a humanized monoclonal antibody that binds CD52, an antigen expressed at high density on most normal and malignant T- and B-cell lymphocytes but not on hematopoietic stem cells.1,2 Alemtuzumab has demonstrated consistent activity against malignant lymphocytes in blood, marrow and the spleen. However, its activity is limited by the presence of bulky disease (lymph nodes, extranodal masses), which is often associated with refractory disease. The suggestion that monoclonal antibodies, such as alemtuzumab, might be best utilized under conditions of MRD has prompted several trials investigating the role of alemtuzumab following tumor debulking by chemotherapy.