Immune Checkpoint Immunotherapy for Non-Small Cell Lung Cancer: Benefits and Pulmonary Toxicities

Abstract

Immune checkpoint inhibitors (ICIs) are newer, immunotherapy-based drugs that have been shown to improve survival in advanced non-small cell lung cancer (NSCLC). Unlike traditional chemotherapeutic agents, ICIs work by boosting the body's natural tumor killing response. However, this unique mechanism of action has also led to the recognition of class-specific side effects. Labeled immune-related adverse events, these toxicities can affect multiple organ systems including the lungs. Immune-mediated lung injury because of ICI use, termed checkpoint inhibitor pneumonitis (CIP), occurs in about 3% to 5% of patients receiving ICIs; however, the real-world incidence of this entity may be higher, especially now that ICIs are being used in nonclinical trial settings. In this review, we briefly introduce the biology of ICIs and the indications for ICI use in NSCLC and then discuss the epidemiology and clinical and radiologic manifestations of CIP. Next, we discuss management strategies for CIP, including the current consensus on management of steroid-refractory CIP. Given the nascent nature of this field, we highlight areas of uncertainty and emerging research questions in the burgeoning field of checkpoint inhibitor pulmonary toxicity.

Keywords: NSCLC; immunotherapy; pneumonitis.

Figure 1

Schematic showing the actions of checkpoint PD-1 and its ligands PD-L1 in untreated and ICI-treated NSCLC. Ag = antigen; APC = antigen-presenting cell; ICI = immune checkpoint immunotherapy; NSCLC = non-small cell lung cancer; PD-1 = programmed death-1; PD-L1 = programmed death-ligand 1; TCR = T-cell receptor.