Soluble CTLA-4 as a favorable predictive biomarker in metastatic melanoma patients treated with ipilimumab: an Italian melanoma intergroup study

Italian Melanoma Intergroup (IMI)

Research output: Contribution to journalArticle

Abstract

CTLA-4 blockade by means of ipilimumab (IPI) potentiates the immune response and improves overall survival (OS) in a minority of metastatic melanoma (MM) patients. We investigated the role of soluble CTLA-4 (sCTLA-4) as a possible biomarker for identifying this subset of patients. sCTLA-4 levels were analyzed at baseline in sera from 113 IPI-treated MM patients by ELISA, and the median value (200 pg/ml) was used to create two equally sized subgroups. Associations of sCTLA-4 with best overall response (BOR) to IPI and immune-related adverse events (irAEs) were evaluated through logistic regression. Kaplan-Meier and Cox regression methods were used to analyze OS. A remarkable association between sCTLA-4 levels and BOR was found. Specifically, the proportion of patients with sCTLA-4 > 200 pg/ml in irSD or irPD (immune-related stable or progressive disease) was, respectively, 80% (OR = 0.23; 95%CL = 0.03-1.88) and 89% (OR = 0.11; 95%CL = 0.02-0.71) and was lower than that observed among patients in irCR/irPR (immune-related complete/partial response). sCTLA-4 levels increased during IPI treatment, since the proportion of patients showing sCTLA > 200 pg/ml after 3 cycles was 4 times higher (OR = 4.41, 95%CL = 1.02-19.1) than that after 1 cycle. Moreover, a significantly lower death rate was estimated for patients with sCTLA-4 > 200 pg/ml (HR = 0.61, 95%CL = 0.39-0.98). Higher baseline sCTLA-4 levels were also associated with the onset of any irAE (p value = 0.029), in particular irAEs of the digestive tract (p value = 0.041). In conclusion, our results suggest that high sCTLA-4 serum levels might predict favorable clinical outcome and higher risk of irAEs in IPI-treated MM patients.

Original languageEnglish
Pages (from-to)97-107
Number of pages11
JournalCancer Immunology and Immunotherapy
Volume68
Issue number1
DOIs
Publication statusE-pub ahead of print - Oct 11 2018

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Immunological/therapeutic use
  • Biomarkers, Tumor/blood
  • CTLA-4 Antigen/blood
  • Female
  • Humans
  • Ipilimumab/therapeutic use
  • Italy
  • Kaplan-Meier Estimate
  • Male
  • Melanoma/drug therapy
  • Middle Aged
  • Neoplasm Metastasis
  • Predictive Value of Tests
  • Solubility
  • Young Adult

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