title: Impact of age on outcomes after initial therapy with chemotherapy and different chemoimmunotherapy regimens in patients with chronic lymphocytic leukemia: results of sequential cancer and leukemia group B studies.
abstract: OBJECTIVE
  Chronic lymphocytic leukemia (CLL) is a disease of the elderly, yet few clinical trials include a significant number of older patients, and outcomes after specific therapies can be different depending on age.
  
  
  METHODS
  We examined patients enrolled onto successive first-line CALGB CLL trials to determine whether efficacy of regimens varied by age, focusing on ideal chemotherapy choice and benefit of immunotherapy addition to chemotherapy in older patients. Regimens included chlorambucil, fludarabine, fludarabine plus rituximab (FR), fludarabine with consolidation alemtuzumab, and FR with consolidation alemtuzumab.
  
  
  RESULTS
  A total of 663 patients were evaluated for response, progression-free survival (PFS), and overall survival (OS) by age group. Interaction effects of fludarabine versus chlorambucil by age group (PFS, P = .046; OS, P = .006) showed that among patients younger than 70 years, PFS and OS was improved with fludarabine over chlorambucil (PFS: hazard ratio [HR] = 0.6, 95% CI, 0.5 to 0.8; OS: HR = 0.7, 95% CI, 0.5 to 0.9), but not in older adults (PFS, HR = 1.0, 95% CI, 0.6 to 1.7; OS: HR = 1.5, 95% CI, 0.9 to 2.3). In contrast, FR improved outcomes relative to fludarabine, irrespective of age (PFS: HR = 0.6, 95% CI, 0.4 to 0.7; OS: HR = 0.7, 95% CI, 0.5 to 0.9). Alemtuzumab consolidation did not provide benefit over similar regimens without alemtuzumab (P > .20), irrespective of age.
  
  
  CONCLUSIONS
  These data support the use of chlorambucil as an acceptable treatment for many older patients with CLL and suggest rituximab is beneficial regardless of age. These findings bear relevance to both routine care of CLL patients 70 years and older and also future clinical trials in this population.
authors.affiliation: Ohio State University, Columbus, OH 43210, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Woyach
authors.forename: Amy S
authors.initials: AS
authors.lastname: Ruppert
authors.forename: Kanti
authors.initials: K
authors.lastname: Rai
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Lin
authors.forename: Susan
authors.initials: S
authors.lastname: Geyer
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kolitz
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Belch
authors.forename: Vicki A
authors.initials: VA
authors.lastname: Morrison
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002699:Chlorambucil / Q000008:administration & dosage; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D015999:Multivariate Analysis; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D000069283:Rituximab; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D002699:Chlorambucil; D000074323:Alemtuzumab; D000069283:Rituximab; D014740:Vidarabine; C024352:fludarabine