Abstract Rationale Pembrolizumab is a PD-1 immune checkpoint inhibitor that has demonstrated significant improvements in both overall survival and progression-free survival. While its association with pulmonary toxicities, particularly pneumonitis, is well-documented, the effects of pembrolizumab on acute respiratory distress syndrome (ARDS), pulmonary fibrosis, and pneumonia remain under-researched. Methods We conducted a retrospective cohort study using TriNetX, a federated global research network aggregating de-identified electronic medical records from large healthcare organizations. Adult patients with Lung cancer were included. Patients were stratified into two groups: those who received combination Chemoimmunotherapy (Pembrolizumab with standard chemotherapy regimens) and those who only received standard Chemotherapy regimens. Propensity score matching (1:1) was performed to balance cohorts by age, sex, HF, COPD, Asthma, ILD, Metastatic disease, Prior thoracic radiation, Oxygen dependence and other comorbidities (CKD, Obesity, DM, Nicotine dependence). The primary outcome was the incidence of pulmonary complications including ARDS, Pulmonary fibrosis, Pneumonitis, Viral and Bacterial Pneumonia. Secondary outcomes assessed the severity and risk of 30-day all-cause mortality in patients who developed ARDS. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated to compare event rates between groups at each interval. Results A total of 55,256 patients met the inclusion criteria, with 27,628 in each matched cohort. The mean age was 66.4 years in the Chemoimmunotherapy group and 66.6 years in the control group. Chemoimmunotherapy-treated patients using Pembrolizumab had a significantly lower risk of developing ARDS (RR 0.688, 95% CI 0.571, 0.828, P 0.001), although among patients who developed ARDS, chemoimmunotherapy-treated group had a significantly higher risk of all cause 30-day mortality (RR 1.302, 95% CI 1.069, 1.587, P = 0.008). Chemoimmunotherapy-treated patients also had a significant increase in the risk of developing Pneumonitis (RR 2.898, 95% CI 2.154, 3.895, P 0.001), Viral Pneumonia (RR 1.623, 95% CI 1.441, 1.827, P 0.001) and Bacterial Pneumonia (RR 1.138, 95% CI 1.066, 1.215, P 0.001) with no significant difference in developing Pulmonary Fibrosis (RR 1.003, 95% CI 0.914, 1.101, P = 0.947). Conclusion Although Pembrolizumab plus chemotherapy treatment regimen was associated with lower risk of developing ARDS, patients who developed ARDS on this regimen had a significantly higher risk of short-term mortality, with increased baseline risks of Pneumonitis, Bacterial and Viral Pneumonia. These findings indicate that patients treated with pembrolizumab had worse pulmonary outcomes with increased mortality in patients who developed ARDS, prompting the need for close monitoring. This abstract is funded by: None
Jabiri et al. (Fri,) studied this question.
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