Table 3.
Potential risk factors for checkpoint inhibitor pneumonitis (CIP) in NSCLC.
| Potential risk factors | Details |
|---|---|
| Sex | Males have a higher incidence of CIP |
| Age of patients | ·Patients aged >70 years |
| ·The decreased lung function and increased medical complications in the elderly may be the cause of higher incidence of CIP | |
| Tumor histologic type | A higher incidence of CIP in patients with squamous NSCLC |
| Smoking status | Patients with former or current smoking |
| Prior thoracic | The incidence of CIP is numerically higher in patients receiving chest-RT compared with non-chest/no RT |
| radiation therapy | ·Radiation parameters have no correlation with the development of pneumonitis |
| ·The influence of radiotherapy courses, type and timing for development of CIP is still not clear | |
| ·T cells activated during ICIs treatment are more easily infiltrate into the damaged lung tissue by thoracic irradiation | |
| PD-1 inhibitors | ·The incidence of CIP with PD-1 inhibitors is higher than PD-L1 inhibitors |
| ·PD-1/PD-L1 inhibitors are related to a higher incidence of CIP than anti-CTLA4 | |
| ·PD-1 inhibitors lead to increased risk through increasing the interaction of PD-L2- RGMb | |
| Combination therapy | ·Additional immune-targeted drugs, chemotherapeutic drugs and some specific tyrosine kinase inhibitors (TKIs) |
| ·Combination of PD-1/PD-L1 inhibitors with other antitumor agents might mediate the superposition effect of multiple drugs on pulmonary toxicity | |
| EGFR mutation | Patients with EGFR mutation are more likely to undergo pneumonitis during the combination therapy of ICIs with osimertinib |
| Sequences of drug administration | PD-(L)1 blockade followed by osimertinib is related to a higher incidence of pneumonitis |
| Preexisting lung disease | Pulmonary infection, pulmonary emphysema, COPD, asthma, ILD, pulmonary fibrosis, pneumothorax, and pleural effusion |
| Tumor invasion | ·Tumor invades the central airway was strongly associated with early-onset CIP |
| ·Extrathoracic metastasis was related to a lower incidence of CIP | |
| Baseline peripheral-blood absolute eosinophil count (AEC) | A high level of baseline AEC(≥0.125×109cells/L) correlated with an increasing risk of CIP but a better clinical outcome |
| Baseline level of anti-CD74 autoantibody | A higher baseline level of anti-CD74 autoantibody is also more likely to develop CIP |
NSCLC, non-small-cell lung cancer; CIP, checkpoint inhibitor pneumonitis; RT, radiation therapy; PD-1, programmed cell death protein 1; PD-L1, programmed cell death protein ligand-1; CTLA-4, cytotoxic T lymphocyte-associated protein 4; PD-L2, programmed cell death protein ligand-2; RGMb, repulsive guidance molecule b; TKIs, tyrosine kinase inhibitors; EGFR, epidermal growth factor receptor; COPD, chronic obstructive pulmonary disease; ILD, interstitial lung disease; AEC, absolute eosinophil count.