Monoclonal antibody therapy of chronic lymphocytic leukemia

Cure of patients with chronic lymphocytic leukemia (CLL) has been an elusive goal. The recent availability of active monoclonal antibodies has rekindled enthusiasm for new and innovative therapeutic approaches. Alemtuzumab, induces responses in about a third of patients with relapsed or refractory CLL following therapy with fludarabine and an alkylating agent. Whereas, rituximab has limited activity in previously treated patients, response rates of 50-70% have been reported in those without prior therapy. Recent data on combinations with rituximab and chemotherapy have shown promise for improving patient outcome. Newer antibodies in development include the primatized monoclonal antibody lumiliximab (IDEC-152), directed against CD23. Other biological approaches include the use of antisense oligonucleotides, proapoptic small molecules, and vaccines directed against the malignant B cells. The rational development of combinations of these promising approaches may eliminate the need for chemotherapy, leading to safer and more effective approaches for patients with CLL.