Treatment of B-cell chronic lymphocytic leukemia with nonchemotherapeutic agents: Experience with single-agent and combination therapy

Recent advances in purine analog-based combination chemotherapy and chemoimmunotherapy have significantly improved response rates and progression-free survival in patients with B-cell chronic lymphocytic leukemia (CLL). However, there are clinical scenarios in which purine analog-based treatment may not be appropriate, either because of the risk of toxicity in patients with comorbidity or because purine analog-based therapies are unlikely to achieve satisfactory responses. Novel, nonchemotherapeutic treatment regimens are becoming increasingly important in these patients, as well as in patients in whom combination chemotherapy-based treatment has failed or resulted in relapse. Nonchemotherapeutic agents include monoclonal antibodies, glucocorticoids, immunomodulatory drugs, drugs with specific intracellular molecular targets, vaccines and cellular immunotherapies. These agents use diverse mechanisms of action that may complement each other, therefore providing a scientific rationale to investigate combinations of these agents in the treatment of CLL. In this review, we will discuss current knowledge of available nonchemotherapeutic agents, available clinical experience with their use alone and in combination and how these approaches may affect outcomes in patients with CLL.