Pneumonitis associated with immune checkpoint inhibitor use was found to occur more frequently and was more severe in a real-world cohort compared with what has been previously reported in clinical trials, according to the results from a retrospective study published in Chest.

“Best clinical practices regarding the diagnosis, management, and risk stratification of [immune checkpoint inhibitor]-pneumonitis remains a significant barrier to improved lung cancer treatment and outcomes,” the authors wrote. The aim of this study was to determine the incidence of [immune checkpoint inhibitor]-associated pneumonitis and identify potential risk factors.

The retrospective, case-control study included 315 patients with lung cancer who were treated with an immune checkpoint inhibitor — either nivolumab (76.5%), pembrolizumab (22.2%), or ipilimumab plus nivolumab (1.9%) — primarily in the second line. Patients were recruited from 6 centers in North Carolina, including 4 community-based centers, a community referral center, and an academic center.

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Within the cohort, the median age was 66 years. Half (50.2%) of the patients were men, and 79.0% were White, 18.4% were Black/African American, 0.3% were Asian, and 2.2% were of other race. The majority of patients were ever smokers and 8.9% were never smokers. Pulmonary comorbidities were common, with 40.3% of patients having chronic obstructive pulmonary disease (COPD), 6.7% had asthma, 1.6% had interstitial lung disease, and 2.2% had another pulmonary disorder. Adenocarcinoma histology was present among 93.7%, squamous cell carcinoma was present among 28.5%, and 6.3% of patients had small cell lung cancer.

Immune checkpoint inhibitor-associated pneumonitis developed among 9.5% of patients; the incidence in clinical trials is generally less 5%. Pneumonitis was diagnosed at a median of 52.5 days after the first immune checkpoint inhibitor treatment, with the most common symptoms including shortness of breath (96.7%) and cough (63.3%). Oxygen saturation was less than 88% on room air among 73.7% of patients.

Pneumonitis was considered grade 3 or greater by American Society of Clinical Oncology criteria among more than 50% of cases and 60% required hospitalization. Additional immune-related adverse events were present among 26.7% of patients.

The majority of pneumonitis cases (93.3%) were treated with corticosteroids with a median duration of 30 days and a median cumulative prednisone-equivalent dose of 1350 mg. After corticosteroid tapering, 13.3% of patients experienced worsening of their pneumonitis.

In multivariate analysis, there was a significant increase in the odds of developing immune checkpoint inhibitor-associated pneumonitis among patients with obstructive lung disease (adjusted odds ratio [aOR], 2.79; 95% CI, 1.07-7.29), with fibrosis on baseline chest computed tomographic imaging (aOR, 6.61; 95% CI, 2.48-17.70), and in those undergoing treatment with pembrolizumab rather than nivolumab (aOR, 2.57; 95% CI, 1.08-6.11).

The authors concluded that “these data show that [immune checkpoint inhibitor]-pneumonitis in a real-world lung cancer cohort is more common and severe than previously reported.”


Atchley WT, Alvarez C, Saxena-Beem S, et al. Immune checkpoint inhibitor-related pneumonitis in lung cancer: real-world incidence, risk factors, and management practices across six health care centers in North Carolina. Chest. Published online February 20, 2021. doi:10.1016/j.chest.2021.02.032