Review of Immune-Related Adverse Events (irAEs) in Non-Small-Cell Lung Cancer (NSCLC)—Their Incidence, Management, Multiorgan irAEs, and Rechallenge

Abstract

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced malignancies, including non-small cell lung cancer (NSCLC). These agents have improved clinical outcomes and have become quite an attractive alternative alone or combined with other treatments. Although ICIs are tolerated better, they also lead to unique toxicities, termed immune-related adverse events (irAEs). A reconstituted immune system may lead to dysregulation in normal immune self-tolerance and cause inflammatory side effects (irAEs). Although any organ system can be affected, immune-related adverse events most commonly involve the gastrointestinal tract, endocrine glands, skin, and liver. They can occur anytime during the treatment course and rarely even after completion. Owen and colleagues showed that approximately 30% of patients with NSCLC treated with ICIs develop irAEs. Kichenadasse et al. conducted a thorough evaluation of multiorgan irAEs, which is of particular interest because information regarding these types of irAEs is currently sparse. It is important to delineate between infectious etiologies and symptom progression during the management of irAEs. Close consultation with disease-specific subspecialties is encouraged. Corticosteroids are the mainstay of treatment of most irAEs. Early intervention with corticosteroids is crucial in the general management of immune-mediated toxicity. Grade 1–2 irAEs can be closely monitored; hypothyroidism and other endocrine irAEs may be treated with hormone supplementation without the need for corticosteroid therapy. Moderate-to high-dose steroids and other additional immunosuppressants such as tocilizumab and cyclophosphamide might be required in severe, grade 3–4 cases. Recently, increasing research on irAEs after immunotherapy rechallenge has garnered much attention. Dolladille and colleagues assessed the safety in patients with cancer who resumed therapy with the same ICIs and found that rechallenge was associated with about 25–30% of the same irAEs experienced previously (4). However, such data should be carefully considered. Further pooled analyses may be required before we conclude about ICIs’ safety in rechallenge.