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We conducted a systematic review of the literature (both published and in progress) addressing the immunologic effects of alemtuzumab. Alemtuzumab has been shown to induce prolonged CD20-mediated antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against CD20-expressing chronic lymphocytic leukemia (CLL) cells in vitro, and to inhibit CLL cell growth in xenograft models of human CLL. In addition, alemtuzumab may inhibit CLL cell growth by inducing apoptosis. Alemtuzumab also has the ability to deplete T cells and B cells from patients with CLL. Alemtuzumab has several unique mechanisms of action that may have the potential to improve patient response compared with chlorambucil and fludarabine. Areas covered: In this review, we give an overview of in vitro and in vivo data (phase I/II studies, and retrospective data from phase III trials) addressing the immunologic effects of alemtuzumab. Both published and unpublished data is discussed. Review of the literature was performed from 1991 until 2016. The authors did not apply any language restrictions to the search. Expert commentary: Results from all phase II and phase III studies addressing the immunologic effects of alemtuzumab are reported. The most consistent effects reported with alemtuzumab therapy are the depleting effects on T cells and B cells in CLL patients. These results suggest that alemtuzumab will be a useful addition to the treatment armamentarium for CLL. Whether it will replace chlorambucil or fludarabine will require the results of large phase III trials.Brick Township

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