Checkpoint Inhibitor Pneumonitis: Updates in Management

Checkpoint inhibitor pneumonitis (CIP) is a potentially life-threatening immune-related adverse event associated with immune checkpoint inhibitors (ICIs). While high-dose corticosteroids remain the first-line treatment, up to 40% of patients experience steroid-refractory or resistant disease, posing significant management challenges. This review synthesizes current evidence on evolving CIP management strategies, highlighting both established therapies and emerging options. Recent guidelines favor mycophenolate mofetil (MMF) and intravenous immunoglobulin (IVIG) as second-line agents, replacing infliximab due to infection concerns in this immunocompromised population. Additional therapies such as cyclophosphamide, calcineurin inhibitors, and pulsed-dose corticosteroids have shown benefit in select cases, though evidence remains limited. Advances in understanding CIP immunopathogenesis have spurred interest in targeted biologics, notably interleukin-6 inhibitors like tocilizumab, which demonstrate promise in early reports. Antifibrotic agents, including nintedanib and pirfenidone, are also under investigation for their potential to manage fibrosis, particularly in patients with underlying interstitial lung disease or progressive fibrotic changes. Experimental strategies such as plasmapheresis, granulocyte-macrophage colony-stimulating factor (GM-CSF) modulation, and Janus kinase (JAK) inhibitors are being explored, with several prospective trials underway. Despite these advances, challenges persist in early diagnosis, risk stratification, and the absence of prospective, biomarker-driven treatment algorithms. This review emphasizes the importance of multidisciplinary, individualized management and highlights promising avenues for future research to improve outcomes in this increasingly encountered complication of cancer immunotherapy.