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. LarkinChristian U. Blank*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

213 Citations (Web of Science)

Abstract

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. 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. 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. 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.
Original languageEnglish
Pages (from-to)449-458
JournalCancer Immunology Immunotherapy
Volume63
Issue number5
DOIs
Publication statusPublished - May 2014

Keywords

  • Melanoma
  • Immunotherapy
  • Ipilimumab
  • Lactate dehydrogenase
  • Biomarker

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