Incidence and risk of drug-induced interstitial lung disease associated with anti-neoplastic drugs

Background: To evaluate the incidence and risk of drug-induced interstitial lung disease (DIILD) associated with anti-neoplastic drugs among patients with cancer in Korea. Research design and methods: This nested case-control study included 457,685 patients diagnosed with cancer and treated with anti-neoplastic drugs from a retrospective nationwide population-based cohort between 2017 and 2021. The incidence rate of DIILD and the risks of DIILD by anti-neoplastic drug categories were analyzed. Results: Among 270,595 patients, 2,634 developed ILD, resulting in an incidence rate of 4.12 per 1,000 person-years (95% confidence interval (CI): 3.97–4.28). DIILD was more prevalent in men, older patients, and those with a history of pulmonary disease or lung cancer. In a multivariable conditional logistic regression analysis, immune checkpoint inhibitors (odds ratio (OR): 2.37; 95%CI: 1.48–3.78), mammalian target of rapamycin inhibitors (OR: 9.79; 95%CI: 5.20–18.45), antibody-drug conjugates (OR: 7.99; 95%CI: 3.24–19.74), cyclin-dependent kinase 4/6 inhibitors (OR: 2.28; 95%CI: 1.26–4.12), and any combination of different drug categories (OR: 1.93; 95%CI: 1.21–3.09) were associated with an increased risk of DIILD. Conclusion: Our findings suggest that the risk of incident DIILD depends on the category of anti-neoplastic drugs. Patients with identified risk factors and treated with these drugs should be monitored closely.