Letter Regarding “Impact of Immune-Related Adverse Events on Efficacy of Immune Checkpoint Inhibitors in Patients with Advanced Hepatocellular Carcinoma”

According to the Common Terminology Criteria for Adverse Events v4.03 criteria, grade 3 and above irAEs require hospitalization, among which grade 4 means life-threatening and grade 5 equals death [9]. Since the lethality of grade 4 and 5 might be obscured by the extended survival of grade 3 in the current categorizing strategy, we suggest categorizing irAEs into three classes of grade 1–2, grade 3, and grade 4–5. [...]gender difference in irAEs has rarely been reported in previous ICI cohorts, but a male predilection was reported in this article, which could be a bias due to the male predominance in aHCC. Since irAEs could be censored by disease progression or death, we suggest competing risk analysis instead of standard Cox analysis to identify independent risk factors for irAEs. A recent finding that interleukin-6 blockade reduces irAEs and improves antitumor immunity in the meantime implies the potential dissociation between irAEs and treatment response, making one wonder if irAEs could serve as a time-varying confounder instead of an independent variable in the survival analysis [12].