Risk of elevated transaminases in cancer patients treated with immune checkpoint inhibitors: a meta-analysis

Expert Opin Drug Saf. 2015 Oct;14(10):1507-18. doi: 10.1517/14740338.2015.1085969. Epub 2015 Sep 7.

Abstract

Background: This meta-analysis has been conducted to determine the risk of elevated transaminases associated with immune checkpoint inhibitors use in patients with cancer.

Methods: Studies eligible for our analysis included randomized Phase II and III trials of patients with cancer on ipilimumab, nivolumab, pembrolizumab, tremelimumab and pidilizumab, which describe events of elevated transaminases [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)].

Results: Initial database search revealed 210 relevant citations. After excluding noneligible studies, 10 trials were considered eligible for the quantitative synthesis. The RR of all-grade elevated ALT and AST was 2.36 (95% CI 1.20-4.66; p = 0.01) and 1.53 (95% CI 0.73-3.22; p = 0.26), respectively, whereas for high-grade elevated ALT and AST, it was 11.27 (95% CI 5.38-23.63; p < 0.0001) and 4.9 (95% CI 2.97-8.09; p < 0.0001), respectively.

Conclusions: Our study has shown that the use of immune checkpoint inhibitors has a causal relationship to an increased risk of high-grade elevated ALT and AST. Clinicians using these agents should be attentive of this risk.

Keywords: alanine aminotransferase; aspartate aminotransferase; ipilimumab; nivolumab; pembrolizumab.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Alanine Transaminase / metabolism*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Aspartate Aminotransferases / metabolism*
  • Humans
  • Neoplasms / drug therapy
  • Randomized Controlled Trials as Topic
  • Risk

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Aspartate Aminotransferases
  • Alanine Transaminase