Immunotherapy-related pneumonitis and the synergic impact of thoracic radiation and preexisting interstitial lung disease.

Abstract

Immune checkpoint inhibitors (ICIs) are the frontline of therapy for most cancers. Although ICIs are sometimes considered to be less harmful than systemic chemotherapies, ICIs may cause immune-related adverse events, which are cases of off-target inflammation in healthy tissues. Pneumonitis, an immune-related adverse event, is the leading cause of therapy-related mortality with ICIs. The aim of this review is to discuss how preexisting interstitial lung disease (ILD) and thoracic radiation increase the risk for ICI-pneumonitis. We discuss potential mechanisms of lung injury and how pneumonitis may impact cancer treatments. Preexisting ILD and thoracic radiation are major risk factors for ICI-pneumonitis. The mechanisms of injury are still not fully understood but may involve the same inflammatory and profibrotic cytokines as those seen in sporadic ILD. Thoracic radiation increases the risk for ICI-pneumonitis and may synergize with preexisting ILD to worsen toxicity. Preexisting ILD and thoracic radiation may increase the risk for the future development of ICI-pneumonitis. However, while these should not preclude potentially life-saving immunotherapy, in some cases, an alternative treatment strategy may be advisable. A multidisciplinary approach is required involving oncologists, pulmonologists, and radiation oncologists to guide in the selection of cancer treatment and in the diagnosis and treatment of pneumonitis.