Infusion-Related Reactions from Immune Checkpoint Inhibitors in Solid Tumors: A Proportional and Network...

Area of Science:

• Oncology
• Immunotherapy
• Clinical Trials

Background:

• Infusion-related reactions (IRRs) are common adverse events associated with immune checkpoint inhibitors (ICIs), occurring in up to 20% of administrations.
• The incidence of IRRs significantly varies across different types of ICIs.

Purpose of the Study:

• To systematically compare and report the incidence of IRRs across various immune checkpoint inhibitor (ICI) therapies.
• To identify specific ICI agents and combinations with a higher risk of causing IRRs.

Main Methods:

• A comprehensive literature search was conducted across PubMed/MEDLINE, Embase, and Web of Science for phase 3 randomized controlled trials (RCTs) of ICIs (CTLA-4, PD-1, PD-L1, LAG-3 inhibitors) in solid tumors.
• Network meta-analysis and proportional meta-analysis were employed to compare the odds ratios and pooled incidence of IRRs for ICI monotherapies, dual ICI combinations, and placebo/observation groups.

Main Results:

• Analysis of 61 RCTs (40,872 patients) revealed pooled IRR incidences: PD-1 inhibitors (2.31%), PD-L1 inhibitors (8.27% - avelumab 13.53%), PD-1 plus LAG-3 (5.70%), PD-1 plus CTLA-4 (5.55%), and CTLA-4 inhibitors (1.79%).
• Network meta-analysis indicated significantly higher IRR risk with avelumab (OR 79.26) and atezolizumab (OR 43.99) compared to placebo.
• Avelumab, atezolizumab, and the combination of relatlimab plus nivolumab were ranked as having the greatest risk of treatment-related IRRs.

Conclusions:

• Avelumab exhibits the highest risk of IRRs, followed by atezolizumab and dual ICI therapies.
• This comparative analysis provides crucial insights into ICI-associated IRR incidence, aiding in the identification of specific agents responsible for these reactions.
• Findings are particularly relevant for managing patients receiving combination immunotherapies.