title: Alemtuzumab compared with chlorambucil as first-line therapy for chronic lymphocytic leukemia.
abstract: OBJECTIVE
  We conducted a randomized trial to evaluate the efficacy and safety of intravenous alemtuzumab compared with chlorambucil in first-line treatment of chronic lymphocytic leukemia (CLL).
  
  
  METHODS
  Patients received alemtuzumab (30 mg three times per week, for up to 12 weeks) or chlorambucil (40 mg/m(2) every 28 days, for up to 12 months). The primary end point was progression-free survival (PFS). Secondary end points included overall response rate (ORR), complete response (CR), time to alternative therapy, safety, and overall survival.
  
  
  RESULTS
  We randomly assigned 297 patients, 149 to alemtuzumab and 148 to chlorambucil. Alemtuzumab had superior PFS, with a 42% reduction in risk of progression or death (hazard ratio [HR] = 0.58; P = .0001), and a median time to alternative treatment of 23.3 versus 14.7 months for chlorambucil (HR = 0.54; P = .0001). The ORR was 83% with alemtuzumab (24% CR) versus 55% with chlorambucil (2% CR); differences in ORR and CR were highly statistically significant (P < .0001). Elimination of minimal residual disease occurred in 11 of 36 complete responders to alemtuzumab versus none to chlorambucil. Adverse events profiles were similar, except for more infusion-related and cytomegalovirus (CMV) events with alemtuzumab and more nausea and vomiting with chlorambucil. CMV events had no apparent impact on efficacy.
  
  
  CONCLUSIONS
  As first-line treatment for patients with CLL, alemtuzumab demonstrated significantly improved PFS, time to alternative treatment, ORR and CR, and minimal residual disease-negative remissions compared with chlorambucil, with predictable and manageable toxicity.
authors.affiliation: Leeds Teaching Hospitals National Health Service Trust, Leeds General Infirmary, Leeds, United Kingdom. peter.hillmen@nhs.net
authors.forename: Peter
authors.initials: P
authors.lastname: Hillmen
authors.forename: Aleksander B
authors.initials: AB
authors.lastname: Skotnicki
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
authors.forename: Branimir
authors.initials: B
authors.lastname: Jaksic
authors.forename: Anna
authors.initials: A
authors.lastname: Dmoszynska
authors.forename: Jingyang
authors.initials: J
authors.lastname: Wu
authors.forename: Cynthia
authors.initials: C
authors.lastname: Sirard
authors.forename: Jiri
authors.initials: J
authors.lastname: Mayer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016470:Bacteremia / Q000139:chemically induced; D002699:Chlorambucil / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D002699:Chlorambucil; D000074323:Alemtuzumab