Immune-Related Pneumonitis After Chemoradiotherapy and Subsequent Immune Checkpoint Blockade in Unresectable Stage III Non–Small-Cell Lung Cancer

Approximately one third of patients with non–small-cell lung cancer (NSCLC) present with stage III or locally advanced NSCLC. These patients have historically been managed with chemoradiotherapy. However, outcomes for these patients remain poor, with a 5-year survival rate between 15% and 32%. Immune checkpoint inhibitors have revolutionized the treatment of patients with NSCLC. One such agent, durvalumab, a selective high-affinity human immunoglobulin G1 monoclonal antibody that blocks programmed cell death ligand 1 binding to programmed cell death protein 1 and cluster of differentiation 80, was recently approved in the consolidation setting after completion of definitive platinum-based chemoradiotherapy and has become the current standard of care for patients with stage III locally advanced NSCLC. Immune checkpoint blockade is associated with increased risk of immunotherapy-related adverse events, which can be managed most effectively when detected early, ideally in the context of a multidisciplinary approach. Pneumonitis represents the potentially most severe and life-threatening of all reported immunotherapy-related adverse events, but it is further complicated in the context of recent prior therapies also known to cause pulmonary toxicity, such as radiotherapy. However, there are major gaps in our ability to identify immunotherapy-related pneumonitis and distinguish it from radiation pneumonitis. This review aims to define the key steps in the detection, diagnosis, and treatment of immunotherapy-related pneumonitis.