Management of pulmonary toxicity associated with immune checkpoint inhibitors

Abstract

Immunotherapy has become a standard of care in oncology, following the recent approvals of cytotoxic T-lymphocyte-associated protein-4 and programmed cell death-1 inhibitors in lung cancer, melanoma, renal cell carcinoma, Hodgkin's lymphoma, bladder, head and neck cancers. Besides their efficacy, these agents also generate specific immune-related adverse events. Due to the increasing prescription of immune-checkpoint inhibitors, the incidence of immune toxicity will continue to rise. The awareness of immune-related adverse events is key to ensuring both diagnosis and management of the possible serious adverse events. Although severe immune-related adverse events remain rare, they can lead to discontinued treatment or to death if they are not forecasted and managed properly. Even if lung toxicity is not the most frequent adverse event, it remains critical as it can be life-threatening. Herein, the main aspects of pulmonary toxicity are reviewed and guidelines are also proposed in order to manage the possible side-effects.

FIGURE 1

Main respiratory toxicities linked to immunotherapy.

FIGURE 2

Comparison between three studies: severity grade and radiological patterns. OP: organising pneumoniae; HSP: hypersensitivity pneumonitis; NSIP: non-specific interstitial pneumoniae; GGO: ground-glass opacities; ARDS: acute respiratory distress syndrome. ^#: Common Terminology Criteria for Adverse Events 4:0.

FIGURE 3

Suggested “decision tree” for interstitial lung disease induced by immune-checkpoint inhibitors (ICI) treatment. CT: computed tomography. ^#: progressive cancer lesions, infection, pulmonary embolism or heart failure.

FIGURE 4

Suggested management according to severity grade. Grade 1: asymptomatic, clinical or diagnostic observation only; intervention not indicated; Grade 2: symptomatic, medical intervention indicated; limiting instrumental activities of daily living; Grade 3: severe symptoms; limiting self-care activities of daily living, oxygen indicated; Grade 4: life-threatening respiratory compromise; urgent intervention indicated (e.g. tracheotomy or intubation). ^#: a disorder characterised by inflammation focally or diffusely affecting the lung parenchyma.

FIGURE 5

Interstitial lung disease induced by immune-checkpoint inhibitors improvement after treatment. OP: organising pneumoniae; HSP: hypersensitivity pneumonitis.