title: Expression of CD33 is a predictive factor for effect of gemtuzumab ozogamicin at different doses in adult acute myeloid leukaemia.
abstract: It remains unclear in adult acute myeloid leukaemia (AML) whether leukaemic expression of CD33, the target antigen for gemtuzumab ozogamicin (GO), adds prognostic information on GO effectiveness at different doses. CD33 expression quantified in 1583 patients recruited to UK-NCRI-AML17 (younger adults) and UK-NCRI-AML16 (older adults) trials was correlated with clinical outcomes and benefit from GO including a dose randomisation. CD33 expression associated with genetic subgroups, including lower levels in both adverse karyotype and core-binding factor (CBF)-AML, but was not independently prognostic. When comparing GO versus no GO (n=393, CBF-AMLs excluded) by stratified subgroup-adjusted analysis, patients with lowest quartile (Q1) %CD33-positivity had no benefit from GO (relapse risk, HR 2.41 (1.27-4.56), P=0.009 for trend; overall survival, HR 1.52 (0.92-2.52)). However, from the dose randomisation (NCRI-AML17, n=464, CBF-AMLs included), 6 mg/m2GO only had a relapse benefit without increased early mortality in CD33-low (Q1) patients (relapse risk HR 0.64 (0.36-1.12) versus 1.70 (0.99-2.92) for CD33-high, P=0.007 for trend). Thus CD33 expression is a predictive factor for GO effect in adult AML; although GO does not appear to benefit the non-CBF AML patients with lowest CD33 expression a higher GO dose may be more effective for CD33-low but not CD33-high younger adults.
authors: Department of Clinical Immunology, Institute of Immunology and Immunotherapy, University of Birmingham, Edgbaston, Birmingham, UK.
authors: N
authors: N
authors: Khan
authors: Institute of Cancer and Genetics, Cardiff University School of Medicine, University Hospital Wales, Heath Park, Cardiff, UK.
authors: R K
authors: RK
authors: Hills
authors: Department of Immunology, North Bristol NHS Trust, Bristol, UK.
authors: P
authors: P
authors: Virgo
authors: Institute of Cancer and Genetics, Cardiff University School of Medicine, University Hospital Wales, Heath Park, Cardiff, UK.
authors: S
authors: S
authors: Couzens
authors: Department of Clinical Immunology, Institute of Immunology and Immunotherapy, University of Birmingham, Edgbaston, Birmingham, UK.
authors: N
authors: N
authors: Clark
authors: Institute of Cancer and Genetics, Cardiff University School of Medicine, University Hospital Wales, Heath Park, Cardiff, UK.
authors: A
authors: A
authors: Gilkes
authors: Department of Clinical Immunology, Institute of Immunology and Immunotherapy, University of Birmingham, Edgbaston, Birmingham, UK.
authors: P
authors: P
authors: Richardson
authors: Institute of Cancer and Genetics, Cardiff University School of Medicine, University Hospital Wales, Heath Park, Cardiff, UK.
authors: S
authors: S
authors: Knapper
authors: Department of Medical and Molecular Genetics, King's College London School of Medicine, Guy's and St. Thomas' NHS Foundation Trust, London, UK.
authors: D
authors: D
authors: Grimwade
authors: Department of Haematology, Nottingham University Hospital NHS Trust, Nottingham, UK.
authors: N H
authors: NH
authors: Russell
authors: Institute of Cancer and Genetics, Cardiff University School of Medicine, University Hospital Wales, Heath Park, Cardiff, UK.
authors: A K
authors: AK
authors: Burnett
authors: Department of Clinical Immunology, Institute of Immunology and Immunotherapy, University of Birmingham, Edgbaston, Birmingham, UK.
authors: S D
authors: SD
authors: Freeman
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000617:Aminoglycosides / Q000008:administration & dosage / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000494:pharmacology*; D015415:Biomarkers / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005260:Female; D000079982:Gemtuzumab; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012008:Recurrence; D063268:Sialic Acid Binding Ig-like Lectin 3 / Q000032:analysis*; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000617:Aminoglycosides; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; C571163:CD33 protein, human; D063268:Sialic Acid Binding Ig-like Lectin 3; D000079982:Gemtuzumab