Cancer Immunology, Immunotherapy

, Volume 63, Issue 5, pp 449–458

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

  • Sander Kelderman
  • Bianca Heemskerk
  • Harm van Tinteren
  • Rob R. H. van den Brom
  • Geke A. P. Hospers
  • Alfonsus J. M. van den Eertwegh
  • Ellen W. Kapiteijn
  • Jan Willem B. de Groot
  • Patricia Soetekouw
  • Rob L. Jansen
  • Edward Fiets
  • Andrew J. S. Furness
  • Alexandra Renn
  • Marcin Krzystanek
  • Zoltan Szallasi
  • Paul Lorigan
  • Martin E. Gore
  • Ton N. M. Schumacher
  • John B. A. G. Haanen
  • James M. G. Larkin
  • Christian U. Blank
Original Article

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.

Keywords

Melanoma Immunotherapy Ipilimumab Lactate dehydrogenase Biomarker 

Supplementary material

262_2014_1528_MOESM1_ESM.pdf (584 kb)
Supplementary material 1 (PDF 584 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Sander Kelderman
    • 1
  • Bianca Heemskerk
    • 1
  • Harm van Tinteren
    • 1
  • Rob R. H. van den Brom
    • 2
  • Geke A. P. Hospers
    • 2
  • Alfonsus J. M. van den Eertwegh
    • 3
  • Ellen W. Kapiteijn
    • 4
  • Jan Willem B. de Groot
    • 5
  • Patricia Soetekouw
    • 6
  • Rob L. Jansen
    • 6
  • Edward Fiets
    • 7
  • Andrew J. S. Furness
    • 8
  • Alexandra Renn
    • 8
  • Marcin Krzystanek
    • 9
  • Zoltan Szallasi
    • 9
  • Paul Lorigan
    • 10
  • Martin E. Gore
    • 8
  • Ton N. M. Schumacher
    • 1
  • John B. A. G. Haanen
    • 1
  • James M. G. Larkin
    • 8
  • Christian U. Blank
    • 1
  1. 1.Netherlands Cancer Institute NKI-AVLAmsterdamThe Netherlands
  2. 2.University Medical Center GroningenGroningenThe Netherlands
  3. 3.VU University Medical CenterAmsterdamThe Netherlands
  4. 4.Leiden University Medical CentreLeidenThe Netherlands
  5. 5.Isala ClinicsZwolleThe Netherlands
  6. 6.Maastricht University Medical CenterMaastrichtThe Netherlands
  7. 7.Medical Center LeeuwardenLeeuwardenThe Netherlands
  8. 8.Royal Marsden HospitalLondonUK
  9. 9.Technical University of DenmarkKongens LyngbyDenmark
  10. 10.Christie HospitalManchesterUK

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