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Lactate dehydrogenase as a selection criterion for ipilimumab treatment in metastatic melanoma

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Abstract

Introduction

Ipilimumab, a cytotoxic T lymphocyte-associated antigen-4 blocking antibody, has improved overall survival (OS) in metastatic melanoma in phase III trials. However, about 80 % of patients fail to respond, and no predictive markers for benefit from therapy have been identified. We analysed a ‘real world’ population of patients treated with ipilimumab to identify markers for treatment benefit.

Methods

Patients with advanced cutaneous melanoma were treated in the Netherlands (NL) and the United Kingdom (UK) with ipilimumab at 3 mg/kg. Baseline characteristics and peripheral blood parameters were assessed, and patients were monitored for the occurrence of adverse events and outcomes.

Results

A total of 166 patients were treated in the Netherlands. Best overall response and disease control rates were 17 and 35 %, respectively. Median follow-up was 17.9 months, with a median progression-free survival of 2.9 months. Median OS was 7.5 months, and OS at 1 year was 37.8 % and at 2 years was 22.9 %. In a multivariate model, baseline serum lactate dehydrogenase (LDH) was demonstrated to be the strongest predictive factor for OS. These findings were validated in an independent cohort of 64 patients from the UK.

Conclusion

In both the NL and UK cohorts, long-term benefit of ipilimumab treatment was unlikely for patients with baseline serum LDH greater than twice the upper limit of normal. In the absence of prospective data, clinicians treating melanoma may wish to consider the data presented here to guide patient selection for ipilimumab therapy.

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Acknowledgments

No funds were received to conduct this study. The authors want to acknowledge the members of the Dutch Working Group on Immunotherapy of Oncology (WIN-O) for their assistance in obtaining the data and their constructive discussion concerning the outcomes of this study.

Conflict of interest

G. A. P. Hospers, A. J. M. van den Eertwegh, E. W. Kapiteijn, J. W. de Groot, P. Lorigan, M. E. Gore, J. B. A. G. Haanen, J. M. G. Larkin and C. U. Blank have participated in advisory board meetings of Bristol-Myers Squibb for which the faculty has received compensation. P Lorigan has received support for travel and compensation for educational and speaker bureau activities. J. M. G. Larkin and M. E. Gore acknowledge National Health Service funding to the National Institute for Health Research Biomedical Research Centre at the Royal Marsden Hospital. J. B. A. G. Haanen and T. N. M. Schumacher are members of the Bristol-Meyers Squibb Immuno-Oncology network and have furthermore received a grant for translational research from Bristol-Meyers Squibb. C. U. Blank receives funding for an investigator-initiated study from Bristol-Myers Squibb. All other authors declared that they have no conflict of interest.

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Authors and Affiliations

  1. Netherlands Cancer Institute NKI-AVL, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    Sander Kelderman, Bianca Heemskerk, Harm van Tinteren, Ton N. M. Schumacher, John B. A. G. Haanen & Christian U. Blank

  2. University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands

    Rob R. H. van den Brom & Geke A. P. Hospers

  3. VU University Medical Center, De Boelelaan 1118, 1081 HV, Amsterdam, The Netherlands

    Alfonsus J. M. van den Eertwegh

  4. Leiden University Medical Centre, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands

    Ellen W. Kapiteijn

  5. Isala Clinics, Dokter van Heesweg 2, 8025 AB, Zwolle, The Netherlands

    Jan Willem B. de Groot

  6. Maastricht University Medical Center, P. Debyelaan 25, 6229 HX, Maastricht, The Netherlands

    Patricia Soetekouw & Rob L. Jansen

  7. Medical Center Leeuwarden, Henri Dunantweg 2, 8934 AD, Leeuwarden, The Netherlands

    Edward Fiets

  8. Royal Marsden Hospital, 197 Fulham Road, London, SW3 6JJ, UK

    Andrew J. S. Furness, Alexandra Renn, Martin E. Gore & James M. G. Larkin

  9. Technical University of Denmark, Anker Engelunds Vej 1, 2800, Kongens Lyngby, Denmark

    Marcin Krzystanek & Zoltan Szallasi

  10. Christie Hospital, 550 Wilmslow Road, Manchester, M20 4BX, UK

    Paul Lorigan

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  1. Sander Kelderman
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  2. Bianca Heemskerk
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  8. Jan Willem B. de Groot
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  17. Martin E. Gore
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  18. Ton N. M. Schumacher
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  19. John B. A. G. Haanen
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  20. James M. G. Larkin
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  21. Christian U. Blank
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Corresponding authors

Correspondence to James M. G. Larkin or Christian U. Blank.

Additional information

Bianca Heemskerk and Harm van Tinteren have contributed equally to this work.

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Kelderman, S., Heemskerk, B., van Tinteren, H. et al. Lactate dehydrogenase as a selection criterion for ipilimumab treatment in metastatic melanoma. Cancer Immunol Immunother 63, 449–458 (2014). https://doi.org/10.1007/s00262-014-1528-9

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