Direct and complement dependent cytotoxicity in CLL cells from patients with high-risk early–intermediate stage chronic lymphocytic leukemia (CLL) treated with alemtuzumab and rituximab

The mechanism of cytotoxicity of alemtuzumab and rituximab in chronic lymphocytic leukemia (CLL) is not well understood. We obtained fresh CLL cells from early–intermediate stage high-risk patients just prior to treatment with alemtuzumab and rituximab to study mechanisms of action and resistance. Alemtuzumab had minimal direct cytotoxicity but caused significant complement dependent cytotoxicity (CDC) although a subpopulation of CLL cells had intrinsic resistance. Rituximab had no direct cytotoxicity and caused minimal CDC in cells from most patients. These data suggest that CDC has a therapeutic role in patients treated with alemtuzumab and that measures to decrease resistance to CDC could increase efficacy.