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Acute myeloid leukemia

Expression of CD33 is a predictive factor for effect of gemtuzumab ozogamicin at different doses in adult acute myeloid leukaemia

Leukemia volume 31, pages 1059–1068 (2017)Cite this article

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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/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.

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Acknowledgements

We are grateful to NIHR and Cancer Research UK for research funding for this trial, to Pfizer Japan for supplying Gemtuzumab Ozogamicin at a discounted price, to the staff of the Haematology Trials Office and Cardiff Experimental Cancer Medicine Centre for supporting the trial and to our co-investigators and research nurses who provided diagnostic samples from the NCRI AML Trial centres (listed in Supplementary Appendix).

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Authors and Affiliations

  1. Department of Clinical Immunology, Institute of Immunology and Immunotherapy, University of Birmingham, Edgbaston, Birmingham, UK

    N Khan, N Clark, P Richardson & S D Freeman

  2. Institute of Cancer and Genetics, Cardiff University School of Medicine, University Hospital Wales, Heath Park, Cardiff, UK

    R K Hills, S Couzens, A Gilkes, S Knapper & A K Burnett

  3. Department of Immunology, North Bristol NHS Trust, Bristol, UK

    P Virgo

  4. Department of Medical and Molecular Genetics, King’s College London School of Medicine, Guy’s and St. Thomas’ NHS Foundation Trust, London, UK

    D Grimwade

  5. Department of Haematology, Nottingham University Hospital NHS Trust, Nottingham, UK

    N H Russell

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on behalf of the UK NCRI-AML Study Group

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Correspondence to N Khan.

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AKB has served on advisory boards for Wyeth/Pfizer during the study. The remaining authors declare no conflict of interest.

Additional information

Presented in part as an oral abstract at the 2015 Annual Meeting of the American Society of Hematology, Orlando, Fl, December 5–8, 2015.

Supplementary Information accompanies this paper on the Leukaemia website

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Khan, N., Hills, R., Virgo, P. et al. Expression of CD33 is a predictive factor for effect of gemtuzumab ozogamicin at different doses in adult acute myeloid leukaemia. Leukemia 31, 1059–1068 (2017). https://doi.org/10.1038/leu.2016.309

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