Immune checkpoint inhibitor-related interstitial lung disease in patients with advanced non-small cell lung cancer: systematic review of characteristics, incidence, risk factors, and management

Abstract

Background: Immune checkpoint inhibitors (ICIs) are widely used in cancers with or without other treatments. Immune-related adverse events (irAEs) have been reported as side effects of ICIs and involve various organs. Pneumonitis, which is also called ICI-related interstitial lung disease (ILD), is one of the lifethreatening adverse events. In this report, we reviewed the safety of ICIs and risk factors for ICI-related ILD in non-small cell lung cancer (NSCLC) patients.Methods: Databases (The National Center for Biotechnology Information, PubMed, Cochrane Library, Google Scholar, and Embase) were searched for the literature on pulmonary adverse events and immunotherapy following PRISMA guidelines. All studies published in English between January 2016 and June 2021 were included.Results: One-hundred twenty-five articles were included at final. Pre-existing ILD as well as asthma and chronic obstructive lung disease (COPD) were associated with high risk for the development of ICI-related ILD, however, it did not affect the prognosis. The treatment of ICI-related ILD is different according to the severity grades, which includes discontinuation of ICI, corticosteroids, and for steroid-refractory ILD, other immunosuppressants. Rechallenging of ICI should be carefully considered in selected patients.Discussion: Patients with pre-existing lung disease and poor lung function need more attention for the development of ICI-related ILD. It is necessary to be aware of clinical manifestation of ICI-related ILD with prompt management.

Update on Adjuvant Treatment in Resectable Non-Small Cell Lung Cancer and Potential Biomarkers Predicting Postoperative Relapse

“…Immunotherapy-related adverse events can affect various organs including lung, skin, endocrine organs, gastrointestinal tract, kidney and others [29][30][31] . Evaluation of risk factors associated with immunotherapy-related adverse events, such as autoimmune diseases, or pre-existing interstitial lung disease is important 32,33 , and checking patients' general conditions before the initiation of the immunotherapy-combined adjuvant treatment is necessary to reduce the possibility of immunotherapy-related adverse events. Since, PORT did not show a definite clinical benefit in the majority of patients who underwent complete resection, radiotherapy-induced toxicity should be an important concern.…”

“…Immunotherapy-related AEs can affect various organs including the lung, skin, endocrine organs, gastrointestinal tract, kidney, and others [ 29 - 31 ]. Evaluation of risk factors associated with immunotherapy-related AEs, such as autoimmune diseases, or pre-existing interstitial lung disease is important [ 32 , 33 ], and checking patients’ general conditions before the initiation of the immunotherapy-combined adjuvant treatment is necessary to reduce the possibility of immunotherapy-related AEs.…”

Two autopsied gastric cancer cases of rare drug-induced pneumonia associated with nivolumab plus S-1 and oxaliplatin: a case report

“…Cancer chemotherapy accounts for 23–51% of drug-induced pneumonia cases, and they are sometimes fatal ( 1 ). Especially, prevalence of immune checkpoint inhibitors (ICI)-related interstitial lung disease (ILD) is reported to be 14.6–19.0% in non-small cell lung cancer ( 2 ). Risk factors are smoking history, pre-existing lung disease, previous drug-induced pneumonia, Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 at cancer diagnosis, and advanced stage of the underlying cancer.…”

Common methodological pitfalls in ICI pneumonitis risk prediction studies

“…Since the introduction of ICIs, many studies have been conducted to discover risk factors and to build risk prediction models. Both systematic and non-systematic reviews have been written to identify possible mechanisms for ICI pneumonitis ( 7 ), to summarize risk factors ( 8 ) and to recommend management strategies ( 9 ). A meta-analysis published in 2022 summarized the odds ratios from 35 studies between 2000 and 2022 and identified several risk factors that have significant pooled effect ( Table 1 ) ( 8 ).…”

“…Risk of bias analysis has been reported only in one previous review ( 8 ), which, together with other existing reviews, did not provide any detailed assessment on the methodology or the prevalence of bias-prone practices ( 7 , 9 , 13 – 16 ). Therefore, in the current systematic review, we present a thorough critical appraisal of the methodology of ICI pneumonitis risk factor identification and risk model development studies.…”