title: Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia.
abstract: OBJECTIVE
  There has been little survival improvement in older patients with acute myeloid leukemia (AML) in the last two decades. Improving induction treatment may improve the rate and quality of remission and consequently survival. In our previous trial, in younger patients, we showed improved survival for the majority of patients when adding gemtuzumab ozogamicin (GO) to induction chemotherapy.
  
  
  METHODS
  Untreated patients with AML or high-risk myelodysplastic syndrome (median age, 67 years; range, 51 to 84 years) were randomly assigned to receive induction chemotherapy with either daunorubicin/ara-C or daunorubicin/clofarabine, with (n = 559) or without (n = 556) GO 3 mg/m(2) on day 1 of course one of therapy. The primary end point was overall survival (OS).
  
  
  RESULTS
  The overall response rate was 69% (complete remission [CR], 60%; CR with incomplete recovery [CRi], 9%), with no difference between GO (70%) and no GO (68%) arms. There was no difference in 30- or 60-day mortality and no major increase in toxicity with GO. With median follow-up of 30 months (range, 5.5 to 54.6 months), 3-year cumulative incidence of relapse was significantly lower with GO (68% v 76%; hazard ratio [HR], 0.78; 95% CI, 0.66 to 0.93; P = .007), and 3-year survival was significantly better (25% v 20%; HR, 0.87; 95% CI, 0.76 to 1.00; P = .05). The benefit was apparent across subgroups. There was no interaction with other treatment interventions. A meta-analysis of 2,228 patients in two United Kingdom National Cancer Research Institute trials showed significant improvements in relapse (HR, 0.82; 95% CI, 0.72 to 0.93; P = .002) and OS (HR, 0.88; 95% CI, 0.79 to 0.98; P = .02).
  
  
  CONCLUSIONS
  Adding GO (3 mg/m(2)) to induction chemotherapy reduces relapse risk and improves survival with little increase in toxicity.
authors.affiliation: FMedSci, Department of Haematology, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN United Kingdom. burnettak@cardiff.ac.uk
authors.forename: Alan K
authors.initials: AK
authors.lastname: Burnett
authors.forename: Nigel H
authors.initials: NH
authors.lastname: Russell
authors.forename: Robert K
authors.initials: RK
authors.lastname: Hills
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kell
authors.forename: Sylvie
authors.initials: S
authors.lastname: Freeman
authors.forename: Lars
authors.initials: L
authors.lastname: Kjeldsen
authors.forename: Ann E
authors.initials: AE
authors.lastname: Hunter
authors.forename: John
authors.initials: J
authors.lastname: Yin
authors.forename: Charles F
authors.initials: CF
authors.lastname: Craddock
authors.forename: Inge Hoegh
authors.initials: IH
authors.lastname: Dufva
authors.forename: Keith
authors.initials: K
authors.lastname: Wheatley
authors.forename: Donald
authors.initials: D
authors.lastname: Milligan
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage; D000368:Aged; D000369:Aged, 80 and over; D000617:Aminoglycosides / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000008:administration & dosage; D000077866:Clofarabine; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D000079982:Gemtuzumab; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use; D015994:Incidence; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000401:mortality*; D016017:Odds Ratio; D012074:Remission Induction; D055502:Secondary Prevention; D016896:Treatment Outcome
chemical_list: D000227:Adenine Nucleotides; D000617:Aminoglycosides; D061067:Antibodies, Monoclonal, Humanized; D001087:Arabinonucleosides; D000922:Immunotoxins; D003561:Cytarabine; D000077866:Clofarabine; D000079982:Gemtuzumab; D003630:Daunorubicin