Real-world incidence and impact of pneumonitis in patients with lung cancer treated with immune checkpoint inhibitors: a multi-institutional cohort study

Abstract

BackgroundImmune checkpoint inhibitors (ICIs) have improved survival and are increasingly used for non-small cell lung cancer. However, use may be limited by immune-related adverse events such as checkpoint-inhibitor pneumonitis (CIP). Literature estimates for CIP incidence are inconsistent. Real-world adherence to guidelines, clinical course, and healthcare utilization in the treatment of CIP has not been described in large cohorts.MethodsA combined claims and electronic health record database (TriNetX) was used to identify 13,113 patients with lung cancer treated with programmed cell death receptor/ligand 1 (PD-1/PD-L1) inhibitors, and a propensity score-matched control cohort treated with chemotherapy or targeted therapies. The attributable risk of CIP was calculated in the first 12 months after therapy by comparing the incidence of diagnosis codes for pneumonitis/pneumonia between cohorts. Cases of CIP, identified by the most specific code for drug-induced respiratory conditions, were further analyzed for medication usage, rates of diagnostic bronchoscopy, ICI discontinuation rates, and usage of hospital services compared with patients receiving PD-1/PD-L1 inhibitors who did not develop CIP.ResultsThe attributable risk of pneumonitis to PD-1/PD-L1 inhibitors was 2.49% (95% CI, 1.50% to 3.47%). Median time to onset in the CIP subcohort was 3.9 months (IQR, 2.1–7.3 months). Steroid and antibiotic use increased dramatically after a pneumonitis diagnosis, and 70.2% of patients permanently discontinued ICI therapy. Compared with controls, patients with CIP had more than a threefold increased risk of needing critical care (relative risk 3.59, 95% CI, 2.31 to 5.57) and an increased risk of mortality (HR 2.34, 95% CI, 1.47 to 3.71).ConclusionsIn a large claims-based analysis, PD-1/PD-L1 inhibitors increase the risk of pneumonitis in patients with lung cancer by 2.49%. Cases of CIP are associated with high healthcare utilization, discontinuation of ICIs, and mortality.

Predictive factors and prognosis of immune checkpoint inhibitor-related pneumonitis in non-small cell lung cancer patients

“…Some clinical trials and reports have shown that the incidence of CIP is approximately 5% ( 18 , 19 ). A multi-institutional cohort study recently has found that the risk of pneumonitis associated with PD-1/PD-L1 inhibitors compared with non-immunotherapy was 2.49% (95% CI: 1.50%-3.47%), and the median time to the onset of CIP was 3.9 months (IQR: 2.1-7.3) ( 20 ). In our study, the median time to the occurrence of CIP was 109 days (IQR: 30-221) after ICI treatment, and the incidence of CIP was approximately 18.5%.…”

Six-week oral prednisolone therapy for immune-related pneumonitis: a single-arm phase II study

“…5 6 However, irP is not uncommon in a real-world setting, and the incidence and mortality of irP is reported to range from 5% to 19% and from 2% to 27%, respectively. [7][8][9][10][11][12][13][14] Thus, cancer therapy is often interrupted because of treatment for irP, even if patients avoid a fatal outcome. 7 Treatment of irP has not been evaluated in any prospective trials, and there is no standardized, evidence-based treatment approach for irP.…”

Characterization of TCF‐1 and its relationship between CD8+ TIL densities and immune checkpoints and their joint influences on prognoses of lung adenocarcinoma patients

“…The staining positivity was determined by the following formula: overall score = percentage score  intensity score. The total score ranged from 0 to 12, with negative staining (0-1) and positive expression (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) of TCF-1. The cutoff score for PD-1 was ≥8% staining according to a previous study.…”

“…Approximately 60% are lung adenocarcinomas, and most are diagnosed at a later stage 2,3 . Based on surgical resection findings, postoperative adjuvant therapy is usually required, which includes chemotherapy, radiotherapy, targeted therapy, and immunotherapy 4–8 . Recently, immunotherapy has been improved due to the rapid clinical development of effective immune checkpoint inhibitors (ICIs) such as T lymphocyte‐associated antigen‐4 (CTLA‐4), programmed cell death 1 (PD‐1), and its ligand (PD‐L1) 9,10 .…”