Expression of CD33 is a predictive factor for effect of Gemtuzumab Ozogamicin at different doses in adult acute myeloid leukemia

Research output: Contribution to journalArticle

Authors

  • P Virgo
  • Steven Knapper
  • David Grimwade
  • N. H. Russell
  • AK Burnett

Colleges, School and Institutes

External organisations

  • Cardiff University
  • Nottingham University Hospitals NHS Trust
  • North Bristol NHS Trust

Abstract

It remains unclear in adult acute myeloid leukemia (AML) whether leukemic 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/m2 GO 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.

Details

Original languageEnglish
Pages (from-to)1059-1068
JournalLeukemia
Volume31
Issue number5
Early online date31 Oct 2016
Publication statusPublished - May 2017

Keywords

  • acute myeloid leukaemia , cancer immunotherapy