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.
Lin
Thomas S
TS
GlaxoSmithKline, Collegeville, PA 19426, USA. thomas.s.lin@gsk.com
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D016503:Drug Delivery Systems; D015507:Drugs, Investigational / Q000627:therapeutic use*; D005419:Flavonoids / Q000627:therapeutic use; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D000077269:Lenalidomide; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D010880:Piperidines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors; D013792:Thalidomide / Q000031:analogs & derivatives / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D015507:Drugs, Investigational; D005419:Flavonoids; D007155:Immunologic Factors; D009363:Neoplasm Proteins; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; C077990:alvocidib; D013792:Thalidomide; D000077269:Lenalidomide