title: Consolidation therapy with subcutaneous alemtuzumab after fludarabine and rituximab induction therapy for previously untreated chronic lymphocytic leukemia: final analysis of CALGB 10101.
abstract: OBJECTIVE
  To determine if alemtuzumab consolidation improves response rate and progression-free survival (PFS) after induction chemoimmunotherapy in previously untreated symptomatic patients with chronic lymphocytic leukemia.
  
  
  METHODS
  Patients (n = 102) received fludarabine 25 mg/m(2) intravenously days 1 to 5 and rituximab 50 mg/m(2) day 1, 325 mg/m(2) day 3, and 375 mg/m(2) day 5 of cycle 1 and then 375 mg/m(2) day 1 of cycles 2 to 6; fludarabine plus rituximab (FR) administration was repeated every 28 days for six cycles. Three months after completion of FR, patients with stable disease or better response received subcutaneous alemtuzumab 3 mg day 1, 10 mg day 3, and 30 mg day 5 and then 30 mg three times per week for 5 weeks.
  
  
  RESULTS
  Overall response (OR), complete response (CR), and partial response (PR) rates were 90%, 29%, and 61% after FR, respectively; 15% of patients were minimal residual disease (MRD) negative. Of 102 patients, 58 received alemtuzumab; 28 (61%) of 46 patients achieving PR after FR attained CR after alemtuzumab. By intent to treat (n = 102), OR and CR rates were 90% and 57% after alemtuzumab, respectively; 42% of patients became MRD negative. With median follow-up of 36 months, median PFS was 36 months, 2-year PFS was 72%, and 2-year OS was 86%. In patients achieving CR after FR, alemtuzumab was associated with five deaths resulting from infection (viral and Listeria meningitis and Legionella, cytomegalovirus, and Pneumocystis pneumonias), which occurred up to 7 months after last therapy. The study was amended to exclude CR patients from receiving alemtuzumab.
  
  
  CONCLUSIONS
  Alemtuzumab consolidation improved CR and MRD-negative rates after FR induction but caused serious infections in patients who had already achieved CR after induction and did not improve 2-year PFS or survival.
authors.affiliation: The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Lin
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Donohue
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.forename: Margaret S
authors.initials: MS
authors.lastname: Lucas
authors.forename: Eva E
authors.initials: EE
authors.lastname: Hoke
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Bengtson
authors.forename: Kanti R
authors.initials: KR
authors.lastname: Rai
authors.forename: James N
authors.initials: JN
authors.lastname: Atkins
authors.forename: Brian K
authors.initials: BK
authors.lastname: Link
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000074323:Alemtuzumab; D000740:Anemia / Q000139:chemically induced; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D018365:Neoplasm, Residual / Q000188:drug therapy; D012074:Remission Induction; D000069283:Rituximab; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; D000074323:Alemtuzumab; D000069283:Rituximab; D014740:Vidarabine; C024352:fludarabine