Omar Abdel-Rahman1, Hesham ElHalawani1, Mona Fouad2. 1. a 1 Ain Shams University, Clinical Oncology Department , Cairo, Egypt +33028656 ; omar.abdelrhman@med.asu.edu.eg. 2. b 2 Ain Shams University, Medical Microbiology and Immunology Department , Cairo, Egypt.
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.
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.
Authors: Li Li; Henry Mok; Pavan Jhaveri; Mark D Bonnen; Andrew G Sikora; N Tony Eissa; Ritsuko U Komaki; Yohannes T Ghebre Journal: Expert Rev Anticancer Ther Date: 2018-07-23 Impact factor: 4.512