Alemtuzumab in peripheral T-cell malignancies

The humanized monoclonal antibody CAMPATH-1H (alemtuzumab) binds to the CD52 antigen, a glycoprotein that is widely expressed on normal and malignant B- and T-lymphocytes. Over the past 5 years, a number of trials have demonstrated that alemtuzumab has clinical activity in mature T-cell diseases such as T-cell prolymphocytic leukemia (T-PLL) and cutaneous T-cell lymphoma (CTCL). In heavily pretreated relapsed/refractory patients alemtuzumab induced responses in more than two thirds of T-PLL and more than 50% of CTCL patients. Responding patients had improved survival compared to nonresponders. Alemtuzumab is particularly effective in clearing malignant lymphocytes from peripheral blood and bone marrow and may therefore facilitate stem-cell transplantation (SCT) in selected patients. The toxicity profile for the antibody is acceptable; the major complications are infusional reactions, which generally subside after the first 1-2 weeks of therapy, and prolonged lymphopenia associated with reactivation of viruses. These can be minimized by careful monitoring and the use of prophylactic therapy. Future studies will be directed toward: alternative routes (subcutaneous) and schedules of administration; use as first-line therapy; combination strategies with conventional chemotherapy; and use of alemtuzumab to purge minimal residual bone-marrow disease prior to SCT.