Chronic lymphocytic leukemia: current and emerging treatment approaches.
In the last decade, advances in the treatment of patients with chronic lymphocytic leukemia (CLL) have improved responses and survival outcomes dramatically. Chlorambucil had been the cornerstone of treatment for decades. Now, treatment approaches typically include a purine nucleoside analog, such as fludarabine, in combination with immunotherapy, most commonly rituximab but also alemtuzumab. Several clinical trials of patients with untreated CLL have reported overall response rates as high as 95% with chemoimmunotherapy. Combinations include fludarabine, cyclophosphamide, and rituximab (FCR); pentostatin, cyclophosphamide, and rituximab; fludarabine and rituximab; and fludarabine and alemtuzumab. FCR has demonstrated complete response rates of 70% as frontline therapy. In addition, molecular prognostic indicators, such as IgVH mutational status, ZAP-70 expression, and chromosomal mutations (trisomy 12; 17p, and 11q deletions) are proving useful in identifying patients with poor-risk disease. Furthermore, advanced technologies such as polymerase chain reaction and flow cytometry can be used to detect minimal residual disease with increasing sensitivity. Elimination of minimal residual disease has been linked to improved survival and become an important clinical goal. While overall response rates with current chemotherapy treatments are superior to those seen with single agents (eg, chlorambucil), many CLL patients still fall short of achieving a complete response. Novel agents with unique, nonoverlapping mechanisms of action (eg, oblimersen sodium, lenalidomide, HuMax-CD20, GX15-070), and other treatments are under investigation in an attempt to further improve outcomes.
Kay
Neil E
NE
Mayo Clinic College of Medicine, Rochester, Minn, USA.
Rai
Kanti R
KR
O'Brien
Susan
S
D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002699:Chlorambucil / Q000627:therapeutic use; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics / Q000378:metabolism; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D015996:Survival Rate; D014314:Trisomy / Q000235:genetics; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000096:biosynthesis / Q000235:genetics
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D002699:Chlorambucil; D000074323:Alemtuzumab; D003520:Cyclophosphamide; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D014740:Vidarabine; C024352:fludarabine