Immune Checkpoint Inhibitor-Induced Insidiously Progressive, Fatal Interstitial Lung Disease

Area of Science:

• Oncology
• Pulmonology
• Immunology

Background:

• Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs), including interstitial lung diseases (ILDs).
• The clinical presentation of ICI-induced ILD (ICI-ILD) is variable.
• A specific focus on insidiously progressive ICI-ILD is warranted due to its potential severity.

Purpose of the Study:

• To investigate the clinical features of ICI-ILD.
• To characterize the subset of patients experiencing insidiously progressive ICI-ILD.
• To identify factors associated with ICI-ILD and its outcomes.

Main Methods:

• Retrospective analysis of 232 advanced lung cancer patients treated with ICIs.
• Identification and classification of immune-related adverse events, specifically ICI-ILD.
• Comparison of clinical features and survival between ICI-ILD and non-irAE groups.

Main Results:

• ICI-ILD occurred in 17.7% of patients and was associated with improved response rates, progression-free survival (PFS), and overall survival compared to the non-irAE group.
• A subset of patients experienced fatal, insidiously progressive ICI-ILD with a median PFS of 7.2 months.
• Insidiously progressive ICI-ILD often presented with a non-organizing pneumonia pattern, weak corticosteroid response, and gradual increases in C-reactive protein and ILD extent during continued ICI treatment.

Conclusions:

• Insidiously progressive ICI-ILD poses a significant risk and can lead to fatal respiratory failure.
• Early identification and discontinuation of ICIs upon recognition of insidious ICI-ILD are critical for potentially improving patient outcomes.
• Understanding the diverse patterns of ICI-ILD is essential for timely management.