New agents in chronic lymphocytic leukemia

Despite advances in treatment, chronic lymphocytic leukemia (CLL) remains incurable with standard therapies. Novel therapeutic agents are needed, particularly for patients with high-risk cytogenetic abnormalities such as del(17p13). The past year has seen several advances in this field. The immunomodulatory drug lenalidomide and the cyclin-dependent kinase inhibitor flavopiridol demonstrated clinical activity in fludarabine-refractory CLL patients with high-risk cytogenetic features and bulky lymphadenopathy, but they were associated with toxicities such as tumor flare and tumor lysis. Second-generation monoclonal anti-CD20 antibodies in clinical trials include ofatumumab, which demonstrated activity in fludarabine-refractory patients with bulky lymphadenopathy. Oblimersen, obatoclax, and ABT-263 target the antiapoptotic protein Bcl-2. Investigational agents with novel therapeutic targets include the anti-CD37 small modular immunopharmaceutical TRU-016, the oral spleen tyrosine kinase (Syk) inhibitor fostamatinib, and the oral phosphatidylinositol-3-kinase (PI3K) inhibitor CAL-101; all of these have all shown preliminary evidence of clinical activity. The development of novel agents for treating CLL remains an active, exciting area of research.