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Acute Leukemias

The addition of gemtuzumab ozogamicin to low-dose Ara-C improves remission rate but does not significantly prolong survival in older patients with acute myeloid leukaemia: results from the LRF AML14 and NCRI AML16 pick-a-winner comparison

Leukemia volume 27, pages 75–81 (2013)Cite this article

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Abstract

The treatment of older patients with acute myeloid leukaemia, who are not considered suitable for conventional intensive therapy, is unsatisfactory. Low-dose Ara-C(LDAC) has been established as superior to best supportive care, but only benefits the few patients who enter complete remission. Alternative or additional treatments are required to improve the situation. This randomised trial compared the addition of the immunoconjugate, gemtuzumab ozogamicin (GO), at a dose of 5 mg on day 1 of each course of LDAC, with the intention of improving the remission rate and consequently survival. Between June 2004 and June 2010, 495 patients entered the randomisation. The addition of GO significantly improved the remission rate (30% vs 17%; odds ratio(OR) 0.48 (0.32–0.73); P=0.006), but not the 12 month overall survival (25% vs 27%). The reason for the induction benefit failing to improve OS was two-fold: survival of patients in the LDAC arm who did not enter remission and survival after relapse were both superior in the LDAC arm. Although the addition of GO to LDAC doubled the remission rate it did not improve overall survival. Maintaining remission in older patients remains elusive.

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Acknowledgements

We are grateful to Wyeth for the provision of gemtuzumab ozogamicin, the Leukaemia Research Fund (now Leukaemia and Lymphoma Research) and Cancer Research UK for research funding, and also to the trial investigators, research colleagues and patients for supporting this investigation. The trial staff at the Birmingham Clinical Trials Unit performed the trial management activity.

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Authors and Affiliations

  1. Department of Haematology, Cardiff University School of Medicine, Cardiff, UK

    A K Burnett & R K Hills

  2. Department of Haematology, Leicester Royal Infirmary, Leicester, UK

    A E Hunter

  3. Department of Haematology, Birmingham Heartlands Hospital, Birmingham, UK

    D Milligan

  4. Department of Haematology, University Hospital of Wales, Cardiff, UK

    W J Kell

  5. CRUK Clinical Trials Unit, University of Birmingham, Birmingham, UK

    K Wheatley

  6. Department of Haematology, Manchester Royal Infirmary, Manchester, UK

    J Yin

  7. Department of Haematology, Belfast City Hospital, Belfast, UK

    M F McMullin

  8. Department of Haematology, Queen Alexandra Hospital, Portsmouth, UK

    H Dignum

  9. Department of Haematology, Leeds Teaching Hospitals NHS Trust, Leeds, UK

    D Bowen

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

    N H Russell

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  1. A K Burnett
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on behalf of the UK National Cancer Research Institute AML Working Group

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Correspondence to A K Burnett.

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Competing interests

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

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Burnett, A., Hills, R., Hunter, A. et al. The addition of gemtuzumab ozogamicin to low-dose Ara-C improves remission rate but does not significantly prolong survival in older patients with acute myeloid leukaemia: results from the LRF AML14 and NCRI AML16 pick-a-winner comparison. Leukemia 27, 75–81 (2013). https://doi.org/10.1038/leu.2012.229

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