Abstract Rationale Immune checkpoint inhibitors, particularly nivolumab, have transformed the management of advanced lung cancer by improving overall survival. However, their pulmonary safety profile—especially in patients who develop acute respiratory distress syndrome (ARDS)—remains incompletely characterized in real-world populations. Understanding ARDS-related mortality and pulmonary complication patterns in nivolumab-treated patients is essential to guide clinical decision-making and optimize management in this vulnerable population. Methods A retrospective cohort study was conducted using the TriNetX Global Collaborative Network, encompassing data from 162 healthcare organizations worldwide. Adults (≥18 years) with lung cancer (ICD-10 C34) were stratified into cohorts based on systemic therapy: nivolumab monotherapy, nivolumab plus chemotherapy, or chemotherapy alone. Patients who developed ARDS were included in mortality analyses. Propensity score matching (1:1) was performed for age, sex, comorbidities, metastatic disease, and prior irradiation. Outcomes included 30-day mortality after ARDS and pulmonary complications (pneumonitis, pulmonary fibrosis, bacterial and viral pneumonia). Risks, risk differences, and odds ratios were calculated with 95% confidence intervals; statistical significance was defined as p 0.05. Results In matched analyses of lung cancer patients who developed ARDS after treatment with nivolumab, chemotherapy, or their combination, distinct survival and pulmonary patterns were observed. Among ARDS cohorts, 99 received nivolumab plus chemotherapy and 99 received chemotherapy alone, while 35 received nivolumab monotherapy and 35 received chemotherapy alone. Thirty-day mortality was higher with nivolumab plus chemotherapy (50.5% vs 32.3%; risk difference 0.18, 95% CI 0.05–0.32, p = 0.009) and higher but not significant with nivolumab monotherapy (62.9% vs 45.7%; p = 0.15). In broader outcome cohorts (n = 9,995 per group for combination; n = 5,083 per group for monotherapy), ARDS incidence was similar across groups. Pulmonary fibrosis and viral pneumonia rates were comparable, bacterial pneumonia occurred less often with nivolumab, and pneumonitis was more frequent in nivolumab-treated cohorts. Overall, nivolumab regimens were not associated with higher ARDS or infection risk but were linked to increased 30-day mortality in patients who developed ARDS. Conclusion Among lung cancer patients who developed ARDS, short-term mortality was significantly higher with nivolumab plus chemotherapy and numerically higher, though not significant, with nivolumab monotherapy compared with chemotherapy alone. Nivolumab-based therapy did not increase the risk of ARDS, pulmonary fibrosis, or infectious pneumonias, although pneumonitis was more frequent across nivolumab groups. These findings indicate that while nivolumab is generally safe, ARDS during treatment may predict worse early outcomes and warrants close monitoring. This abstract is funded by: None
Nada et al. (Fri,) studied this question.