Alemtuzumab use in relapsed and refractory chronic lymphocytic leukemia: a history and discussion of future rational use

In this review, we outline the clinical experience with single-agent alemtuzumab as a treatment for relapsed and refractory chronic lymphocytic leukemia (CLL) in both prospective and retrospective trials and describe the multiagent use of the drug with the goal of updating clinicians on recent developments and possible future rational combinations. Alemtuzumab, an antibody targeting the lymphocyte-specific surface marker CD52, is an approved agent for the treatment of CLL. Despite its demonstrated efficacy, likely secondary to concerns regarding infectious complications, it is most commonly used in the relapsed and refractory setting. Given alemtuzumab's unique mechanism of action it has been demonstrated to have activity in disease that is refractory to both alkylating agents and purine analogs. Furthermore, it has activity in TP53-mutated disease, which has the worst prognosis of any subset of CLL. Alemtuzumab has greater efficacy on circulating disease relative to nodal disease. Rational combinations are attempting to use these attributes to increase response rates in patients with relapsed and refractory disease.