Original Article

Cancer Immunology, Immunotherapy

, Volume 63, Issue 5, pp 449-458

First online:

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

  • Sander KeldermanAffiliated withNetherlands Cancer Institute NKI-AVL
  • , Bianca HeemskerkAffiliated withNetherlands Cancer Institute NKI-AVL
  • , Harm van TinterenAffiliated withNetherlands Cancer Institute NKI-AVL
  • , Rob R. H. van den BromAffiliated withUniversity Medical Center Groningen
  • , Geke A. P. HospersAffiliated withUniversity Medical Center Groningen
  • , Alfonsus J. M. van den EertweghAffiliated withVU University Medical Center
  • , Ellen W. KapiteijnAffiliated withLeiden University Medical Centre
  • , Jan Willem B. de GrootAffiliated withIsala Clinics
  • , Patricia SoetekouwAffiliated withMaastricht University Medical Center
    • , Rob L. JansenAffiliated withMaastricht University Medical Center
    • , Edward FietsAffiliated withMedical Center Leeuwarden
    • , Andrew J. S. FurnessAffiliated withRoyal Marsden Hospital
    • , Alexandra RennAffiliated withRoyal Marsden Hospital
    • , Marcin KrzystanekAffiliated withTechnical University of Denmark
    • , Zoltan SzallasiAffiliated withTechnical University of Denmark
    • , Paul LoriganAffiliated withChristie Hospital
    • , Martin E. GoreAffiliated withRoyal Marsden Hospital
    • , Ton N. M. SchumacherAffiliated withNetherlands Cancer Institute NKI-AVL
    • , John B. A. G. HaanenAffiliated withNetherlands Cancer Institute NKI-AVL
    • , James M. G. LarkinAffiliated withRoyal Marsden Hospital Email author 
    • , Christian U. BlankAffiliated withNetherlands Cancer Institute NKI-AVL Email author 

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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.


Melanoma Immunotherapy Ipilimumab Lactate dehydrogenase Biomarker