title: Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531.
abstract: OBJECTIVE
  To improve survival rates in children with acute myeloid leukemia (AML), we evaluated gemtuzumab-ozogamicin (GO), a humanized immunoconjugate targeted against CD33, as an alternative to further chemotherapy dose escalation. Our primary objective was to determine whether adding GO to standard chemotherapy improved event-free survival (EFS) and overall survival (OS) in children with newly diagnosed AML. Our secondary objectives examined outcomes by risk group and method of intensification.
  
  
  METHODS
  Children, adolescents, and young adults ages 0 to 29 years with newly diagnosed AML were enrolled onto Children’s Oncology Group trial AAML0531 and then were randomly assigned to either standard five-course chemotherapy alone or to the same chemotherapy with two doses of GO (3 mg/m2/dose) administered once in induction course 1 and once in intensification course 2 (two of three).
  
  
  RESULTS
  There were 1,022 evaluable patients enrolled. GO significantly improved EFS (3 years: 53.1% v. 46.9%; hazard ratio [HzR], 0.83; 95% CI, 0.70 to 0.99; P.04) but not OS (3 years: 69.4% v. 65.4%; HzR, 0.91; 95% CI, 0.74 to 1.13; P = .39). Although remission was not improved (88% v. 85%; P = .15), posthoc analyses found relapse risk (RR) was significantly reduced among GO recipients overall (3 years: 32.8% v. 41.3%; HzR, 0.73; 95% CI, 0.58 to 0.91; P = .006). Despite an increased postremission toxic mortality (3 years: 6.6% v. 4.1%; HzR, 1.69; 95% CI, 0.93 to 3.08; P = .09), disease-free survival was better among GO recipients (3 years: 60.6% v. 54.7%; HzR, 0.82; 95% CI, 0.67 to 1.02; P = .07).
  
  
  CONCLUSIONS
  GO added to chemotherapy improved EFS through a reduction in RR for children and adolescents with AML.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Gamis
authors.forename: Todd A
authors.initials: TA
authors.lastname: Alonzo
authors.forename: Soheil
authors.initials: S
authors.lastname: Meshinchi
authors.forename: Lillian
authors.initials: L
authors.lastname: Sung
authors.forename: Robert B
authors.initials: RB
authors.lastname: Gerbing
authors.forename: Susana C
authors.initials: SC
authors.lastname: Raimondi
authors.forename: Betsy A
authors.initials: BA
authors.lastname: Hirsch
authors.forename: Samir B
authors.initials: SB
authors.lastname: Kahwash
authors.forename: Amy
authors.initials: A
authors.lastname: Heerema-McKenney
authors.forename: Laura
authors.initials: L
authors.lastname: Winter
authors.forename: Kathleen
authors.initials: K
authors.lastname: Glick
authors.forename: Stella M
authors.initials: SM
authors.lastname: Davies
authors.forename: Patti
authors.initials: P
authors.lastname: Byron
authors.forename: Franklin O
authors.initials: FO
authors.lastname: Smith
authors.forename: Richard
authors.initials: R
authors.lastname: Aplenc
mesh_terms: D000293:Adolescent; D000328:Adult; D000617:Aminoglycosides / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002170:Canada / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D000079982:Gemtuzumab; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D007223:Infant; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D012008:Recurrence; D033581:Stem Cell Transplantation; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000617:Aminoglycosides; D061067:Antibodies, Monoclonal, Humanized; D000079982:Gemtuzumab
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