Monoclonal antibody combinations in CLL: evolving strategies

Monoclonal antibodies have led to a profound shift in the therapeutic landscape of chronic lymphocytic leukemia (CLL). Alemtuzumab and rituximab remain the most active antibodies, and their single-agent activity has been established in previously untreated and relapsed patients with CLL. Higher response rates and a better quality of response through eradication of minimal residual disease have been reported with monoclonal antibody combinations. Chemoimmunotherapy regimens are being actively explored in frontline CLL therapy, and numerous combination regimens have been investigated in relapse. New and more effective therapies are shifting the focus from palliation to treatment algorithms with curative attempt. Challenges for monoclonal antibody combinations in the future include: (1) defining appropriate patient populations for combination therapies; (2) assessing the impact of pretreatment biologic prognostic factors; (3) enhancing eradication of minimal residual disease; and (4) reassessing response criteria in CLL.