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Biomarkers Associated with Clinical Outcome of Advanced Melanoma Patients Treated with Ipilimumab


Ipilimumab was the first immunotherapy approved for metastatic melanoma in decades and is currently registered as a second-line treatment. However, new immunotherapies, in combination with ipilimumab, offer even better clinical outcomes for patients compared with single-agent treatments, at the expense of improved toxicity. The aim of this study was to evaluate the feasibility of ipilimumab outside the clinical trials and to identify survival predictors for treatment benefit. Data were collected on 47 advanced melanoma patients treated with ipilimumab between 2010 and 2015 at a single center. Association of clinical characteristics (including primary tumor characteristics), serum lactate dehydrogenase (LDH), erythrocyte sedimentation rate, absolute eosinophil, lymphocyte, and neutrophil count, neutrophil/lymphocyte and eosinophil/lymphocyte ratio with toxicity and clinical outcome were assessed using univariate and multivariate analysis. Median progression-free survival at a median follow-up of 10 months was 2.7 months and median overall survival was 9.8 months. Objective response was observed in 17% of patients and the disease control rate at week 24 was 40%. The 1- and 2-year survival rates documented were 40 and 28%, respectively. Significant association between high LDH level (>1.5× upper limit of normal) and decreased overall survival was demonstrated in uni- and multivariate analysis (hazard ratio [HR]: 3.554, 95% CI: 1.225–10.306, p = 0.019). Neither biomarkers nor clinical outcome were associated with toxicity. Using baseline serum LDH to identify patients most likely to benefit from ipilimumab therapy could serve as a simple and inexpensive biomarker of clinical outcome.

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The study was supported by the National Research, Development and Innovation Office grant NKFI K105132.

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Correspondence to Tímea Balatoni.

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Conflicts of Interest

Tímea Balatoni has received speaker honoraria and financial support for attending symposia from Bristol-Myers Squibb, Merck Sharp & Dohme (MSD), Novartis, and Roche. Gabriella Liszkay is on the advisory board and has received honoraria for speaking at conferences as well as financial support for educational programs from Bristol-Myers Squibb, GlaxoSmithKline, MSD, Novartis, and Roche. Gitta Pánczél and Kata Czirbesz has received speaker honoraria from Bristol-Myers Squibb, MSD, Novartis, and Roche. All other authors declare that they have no conflict of interest.

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Balatoni, T., Ladányi, A., Fröhlich, G. et al. Biomarkers Associated with Clinical Outcome of Advanced Melanoma Patients Treated with Ipilimumab. Pathol. Oncol. Res. 26, 317–325 (2020).

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  • Melanoma
  • Ipilimumab
  • Predictive factors
  • Lactate dehydrogenase