Role of CD20 monoclonal antibodies in previously untreated chronic lymphocytic leukemia.

Monoclonal antibodies (MoAbs) directed against the CD20 antigen on B cells have dramatically altered the treatment landscape for patients with chronic lymphocytic leukemia (CLL). Rituximab, a chimeric mouse/human MoAb, was the first antibody to be approved for the treatment of indolent B-cell lymphomas. Although single-agent, standard-dose rituximab has limited activity as first-line therapy for patients with CLL, it has synergistic therapeutic activity when combined with chemotherapy. Indeed, chemoimmunotherapy with combined fludarabine (F), cyclophosphamide (C), and rituximab was shown to improve both progression-free and overall survival in a randomized phase III clinical trial compared with FC in previously untreated patients with CLL. In this article, we review important clinical trials that have incorporated rituximab with other agents for treatment-naive patients with CLL. We also highlight second- and third-generation CD20 MoAbs approved or in development for the treatment of CLL.