Increased risk of Pneumocystis jirovecii pneumonia associated with immune checkpoint inhibitors in lung cancer: a nationwide retrospective cohort study

Although immune checkpoint inhibitors (ICIs) have led to a fundamental shift in lung cancer treatment, evidence regarding infections remains limited. Pneumocystis jirovecii pneumonia (PJP) is a rare but life-threatening opportunistic infection with high mortality if undiagnosed or untreated, making its risk assessment clinically critical. This study aimed to provide population-based comparative evidence on the risk of PJP between ICI therapy and conventional cytotoxic chemotherapy (CC) in patients with lung cancer. Using the Korean nationwide claims data, we conducted a retrospective cohort study of patients newly diagnosed with lung cancer who initiated CC or ICI therapy between 2017 and 2022. After propensity score matching, incidence rate ratios (IRRs), Cox hazard ratios (HRs), and Fine-Gray subdistribution HRs (sHRs) were estimated. Sensitivity analyses were performed across clinically relevant subgroups, including those defined by advanced stage, surgical resection, radiotherapy, treatment line, ICI monotherapy, and systemic corticosteroid use. Additionally, risk patterns across specific ICI agents, including atezolizumab, pembrolizumab, durvalumab, and nivolumab, were evaluated in an exploratory analysis. After matching, 13,426 patients were included in each group. During follow-up, 27 and 66 PJP events occurred in the CC and ICI groups, respectively, corresponding to IRs of 3.35 and 7.77 per 1,000 person-years. ICI therapy was associated with a significantly higher risk of PJP (adjusted IRR 2.26, 95% CI 1.46–3.59; adjusted HR 2.83, 95% CI 1.81–4.44; adjusted sHR 2.63, 95% CI 1.68–4.12). In the exploratory analysis, significantly elevated IRRs, HRs, and sHRs were observed for durvalumab, pembrolizumab, and atezolizumab, while no clear association was observed for nivolumab because of the limited number of events. This association remained robust and consistent across various clinical contexts including cohorts defined by disease stage, treatment line, the use of monotherapy, and patients without systemic steroid exposure. ICI therapy is associated with a significantly increased risk of PJP compared with CC in patients with lung cancer. Given the potential severity of PJP, enhanced clinical vigilance is warranted during ICI treatment.