Management, risk factors and prognostic impact of checkpoint-inhibitor pneumonitis (CIP) in lung cancer – A multicenter observational analysis

• Published in: Lung cancer (Amsterdam, Netherlands) Vol. 179; p. 107184
• Main Authors: Frost, Nikolaj, Unger, Kristina, Blum, Torsten Gerriet, Misch, Daniel, Kurz, Sylke, Lüders, Heike, Olive, Elisabeth, Raspe, Matthias, Hilbrandt, Moritz, Koch, Myriam, Böhmer, Dirk, Senger, Carolin, Witzenrath, Martin, Grohé, Christian, Bauer, Torsten, Modest, Dominik P., Kollmeier, Jens
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.05.2023
• Subjects: Checkpoint-inhibitor pneumonitis; Humans; Immunotherapy; Lung cancer; Lung Neoplasms - drug therapy; PD-L1; Pneumonia - etiology; Prognosis; Retrospective Studies; Risk Factors; Risk Management; Thoracic radiotherapy; Checkpoint-inhibitor pneumonitis; PD-L1; Thoracic radiotherapy; Lung cancer; Immunotherapy
• ISSN: 0169-5002; 1872-8332; 1872-8332
• DOI: 10.1016/j.lungcan.2023.107184

•Incidence of checkpoint inhibitor pneumonitis (CIP) is highest in lung cancer.•CIP mimics features from interstitial and infectious lung diseases.•Incidence in 1.400 German lung cancer patients was 6.0% with 45% high-grade events.•Thoracic radiotherapy directly targeting lung tissue is a key risk factor.•Pretherapeutic diffusion capacity for carbon monoxide is an easy risk assessment. Checkpoint-inhibitor pneumonitis (CIP) represents a major immune-related adverse event (irAE) in patients with lung cancer. We aimed for the clinical characterization, diagnostics, risk factors, treatment and outcome in a large cohort of patients from everyday clinical practice. For this retrospective analysis, 1,376 patients having received checkpoint inhibitors (CPI) in any line of therapy from June 2015 until February 2020 from three large-volume lung cancer centers in Berlin, Germany were included and analyzed. With a median follow-up of 35 months, all-grade, high-grade (CTCAE ≥ 3) and fatal CIP were observed in 83 (6.0%), 37 (2.7%) and 12 (0.9%) patients, respectively, with a median onset 4 months after initiation of CPI therapy. The most common radiologic patterns were organizing pneumonia (OP) and non-specific interstitial pneumonia (NSIP) (37% and 31%). All except 7 patients with G1-2 CIP interrupted treatment. Corticosteroids were administered to 74 patients with a median starting dose of 0.75 mg/kg. After complete restitution (n = 67), re-exposure to CPI (n = 14) led to additional irAE in 43% of the cases. Thoracic radiotherapy targeting the lung was the only independent risk factor for CIP (odds ratio 2.8, p < 0.001) and pretherapeutic diffusing capacity for carbon monoxide inversely correlated with CIP severity. Compared with patients without CIP and non-CIP irAE, CIP was associated with impaired overall survival (hazard ratios 1.23, p = 0.24 and 2.01, p = 0.005). High-grade CIP accounts for almost half of all CIP cases in an allcomer lung cancer population. A continuous vigilance, rapid diagnostics and adequate treatment are key to prevent disease progression associated with impaired survival.