title: Defining the dose of gemtuzumab ozogamicin in combination with induction chemotherapy in acute myeloid leukemia: a comparison of 3 mg/m2 with 6 mg/m2 in the NCRI AML17 Trial.
abstract: Arecent source data meta-analysis of randomized trials in adults assessing the immunoconjugate gemtuzumab ozogamicin combined with standard chemotherapy in acute myeloid leukemia showed a significant survival benefit in patients without an adverse karyotype. It is not clear whether the optimal dose should be 3 mg/m(2) or 6 mg/m(2) In this study, we randomized 788 patients to a single dose of gemtuzumab ozogamicin 3 mg/m(2) or 6 mg/m(2) with the first course of induction therapy. We found that the rate of complete remission was higher with 3 mg/m(2) [82% vs 76%; odds ratio 1.46 (1.04-2.06); P=0.03], but this was balanced by a higher rate of complete remission with incomplete peripheral blood count recovery in the 6 mg/m(2) treatment (10% vs 7%) resulting in similar overall response rate [89% vs 86%; hazard ratio 1.34 (0.88-2.04); P=0.17]. There was no overall difference in relapse or survival at four years between the arms: 46% vs 54%; hazard ratio 1.17 (0.94-1.45), P=0.5, and 50% versus 47%; hazard ratio 1.10 (0.90-1.34), P=0.3, respectively. The 30- and 60-day mortality was significantly higher in the 6 mg/m(2) recipients: 7% versus 3%; hazard ratio 2.07 (1.11-3.87), P=0.02, and 9% versus 5%; hazard ratio 1.99 (1.17-3.39), P=0.01, respectively, which in addition was associated with a higher rate of veno-occlusive disease (5.6% vs 0.5%; P<0.0001). Our conclusion from this trial is that there is no advantage in using a single dose of 6 mg/m(2) of gemtuzumab ozogamicin in combination with induction chemotherapy when compared with a 3 mg/m(2) dose, with respect to response, disease-free and overall survival, either overall, or in any disease subgroup. (AML17 was registered as ISRCTN55675535).
authors.affiliation: Department of Haematology, Cardiff University School of Medicine, UK akburnett719@gmail.com.
authors.forename: Alan
authors.initials: A
authors.lastname: Burnett
authors.affiliation: Department of Haematology, St Bartholomew's Hospital, West Smithfield, London UK.
authors.forename: Jamie
authors.initials: J
authors.lastname: Cavenagh
authors.affiliation: Department of Haematology, Nottingham University Hospital NHS Trust, UK.
authors.forename: Nigel
authors.initials: N
authors.lastname: Russell
authors.affiliation: Department of Haematology, Cardiff University School of Medicine, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Hills
authors.affiliation: Department of Haematology, University Hospital of Wales, Cardiff, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kell
authors.affiliation: Department of Haematology, Newcastle Teaching Hospitals NHS Trust, UK.
authors.forename: Gail
authors.initials: G
authors.lastname: Jones
authors.affiliation: Department of Haematology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Ove Juul
authors.initials: OJ
authors.lastname: Nielsen
authors.affiliation: Department of Haematology, University College, London Cancer Institute, UK.
authors.forename: Asim
authors.initials: A
authors.lastname: Khwaja
authors.affiliation: Department of Haematology, Cardiff University School of Medicine, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Thomas
authors.affiliation: Department of Haematology, Royal Liverpool University Hospital, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Clark
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000617:Aminoglycosides / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D000079982:Gemtuzumab; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012008:Recurrence; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000617:Aminoglycosides; D061067:Antibodies, Monoclonal, Humanized; D000079982:Gemtuzumab