Switching to Immune Checkpoint Inhibitors upon Response to Targeted Therapy; The Road to Long-Term Survival in Advanced Melanoma Patients with Highly Elevated Serum LDH?

Maartje G. Schouwenburg*, Karijn P. M. Suijkerbuijk, Rutger H. T. Koornstra, Anouk Jochems, Michiel C. T. van Zeijl, Alfons J. M. van den Eertwegh, John B. A. G. Haanen, Maureen J. B. Aarts, Alexander C. J. van Akkooi, Franchette W. P. J. van den Berkmortel, Jan Willem B. de Groot, Geke A. P. Hospers, Ellen Kapiteijn, Wim H. Kruit, Djura Piersma, Rozemarijn S. van Rijn, Albert J. ten Tije, Gerard Vreugdenhil, Jacobus J. M. van der Hoeven, Michel W. J. M. Wouters

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

19 Citations (Web of Science)


The prognosis of patients with advanced melanoma has improved dramatically. However, the clinical outcomes of patients with highly elevated serum lactate dehydrogenase (LDH) remain very poor. The aim of this study was to explore whether patients with normalized LDH after targeted therapy could benefit from subsequent treatment with immune checkpoint inhibitors (ICI). Data from all patients with BRAF-mutant metastatic melanoma with a highly elevated serum LDH at baseline (>= 2x upper limit of normal) receiving first-line targeted therapy between 2012 and 2019 in the Netherlands were collected. Patients were stratified according to response status to targeted therapy and change in LDH at start of subsequent treatment with ICI. Differences in overall survival (OS) between the subgroups were compared using log-rank tests. After a median follow-up of 35.1 months, median OS of the total study population (n = 360) was 4.9 months (95% CI 4.4-5.4). Of all patients receiving subsequent treatment with ICI (n = 113), survival from start of subsequent treatment was significantly longer in patients who had normalized LDH and were still responding to targeted therapy compared to those with LDH that remained elevated (median OS 24.7 vs. 1.1 months). Our study suggests that introducing ICI upon response to targeted therapy with normalization of LDH could be an effective strategy in obtaining long-term survival in advanced melanoma patients with initial highly elevated serum LDH.

Original languageEnglish
Article number1940
Number of pages11
Issue number12
Publication statusPublished - Dec 2019


  • melanoma
  • metastasis
  • targeted therapy
  • immune checkpoint inhibitors
  • lactate dehydrogenase
  • real-life data
  • prognostic factors

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