Clinical diagnosis and treatment of immune checkpoint inhibitor‐associated pneumonitis

Wang, Hanping; Guo, Xiaoxiao; Zhou, Jiaxin; Li, Yue; Duan, Lian; Si, Xiaoyan; Zhang, Li; Liu, Xiaowei; Wang, Mengzhao; Shi, Juhong

doi:10.1111/1759-7714.13240

Cited by 67 publications

(67 citation statements)

References 19 publications

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“…Although smoking history was not identified as a risk factor of ICI-ILD in this study, unlike drug-induced ILD 13 , ≥ 50 pack-year was associated with the development of ICI-ILD of all grades. This result suggested that when treating lung cancer with ICI, the presence or absence of smoking history and quantitative assessments of smoking should be considered.…”

Section: Discussioncontrasting

confidence: 65%

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Risk factors of immune checkpoint inhibitor-related interstitial lung disease in patients with lung cancer: a single-institution retrospective study

Okada

Matsuoka

Sakurada

et al. 2020

Sci Rep

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Immune checkpoint inhibitors (ICIs) elicit antitumour effects by activating the host immunity and cause immune-related adverse events (irAes). ici-related interstitial lung disease (ici-iLD) is a fatal irAE that is difficult to treat; moreover, its incidence is relatively higher in patients with lung cancer. therefore, early ici-iLD detection and intervention are important for patient safety. However, a risk assessment method for ici-iLD has not been established and the prediction of ici-iLD occurrence is difficult. The aim of our study was to identify the risk factors associated with ICI-ILD. To this end, we retrospectively analysed 102 patients with lung cancer who first received ICI and completed the treatment between April 2016 and December 2019 at Tokushima University Hospital. Nineteen patients had all grades of ICI-ILD and 10 had grade ≥ 3 ICI-ILD. The 30-day mortality rate of patients with grade ≥ 3 ICI-ILD was the highest among all patients (P < 0.01). The multivariate logistic analysis indicated that the performance status ≥ 2 alone and both performance status ≥ 2 and ≥ 50 pack-year were independent risk factors of ICI-ILD of grade ≥ 3 and all grades, respectively. Overall, our study provides insights to predict ici-iLD occurrence. Immune checkpoint inhibitors (ICIs) are antibodies that inhibit programmed death-1 (PD-1), PD ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), which are called immune checkpoint molecules. These molecules negatively regulate the host immunity; thus, the inhibition of these molecules activates the host immunity and exerts cross-organ antitumour effects 1. In the treatment of lung cancer, some clinical trials have revealed that the administration of ICI alone and in combination with cytotoxic anticancer agents resulted in better clinical outcomes than previous standard treatments; thus, the use of ICI significantly improved lung cancer treatment 2-4. However, the activation of the host immunity by ICI leads to characteristic adverse events, known as immune-related adverse events (irAEs), which exhibit profiles different from those caused by cytotoxic anticancer agents 5,6. Therefore, the management of irAEs is essential for an effective ICI treatment. These irAEs affect various organs, such as the skin, endocrine glands, gastrointestinal tract, and liver, but only a few events are fatal because the majority of them can be controlled by adequate treatment 5,7. Specifically, ICI-related interstitial lung disease (ICI-ILD) has a low incidence (1-5%) and a high severity or mortality rate, according to clinical trials (50-60%) 8,9. Patients with lung cancer are known to have relatively higher ICI-ILD rates than those with other cancers 10. A prospective study of patients with lung cancer reported that the incidence of ICI-ILD was 14.5%, which is higher than that in clinical trials 11. ICI-ILD has also been reported to affect the prognosis of patients with lung cancer 11,12 .

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Section: Discussioncontrasting

confidence: 65%

“…not continue ICI treatment and to achieve treatment benefits in patients with lung cancer. However, only a few studies have reported that the development of ICI-ILD was prevented 13 .…”

mentioning

confidence: 99%

Risk factors of immune checkpoint inhibitor-related interstitial lung disease in patients with lung cancer: a single-institution retrospective study

Okada

Matsuoka

Sakurada

et al. 2020

Sci Rep

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“…However, a specific pattern cannot be defined in some cases [60]. In fact, given the variability of the radiographic features, the possibility of ICI-related pneumonitis should be assessed whenever new non-massive imaging changes are found on chest CT of patients treated with ICI [80]. Special attention should be raised upon the radiologic features that may appear in patients with preexisting lung fibrosis (Fig.…”

Section: Diagnosismentioning

confidence: 99%

Immune Checkpoint Inhibitor-Related Pneumonitis

et al. 2020

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Immune checkpoint inhibitors are novel agents that have been proved efficacious in a variety of cancer types, but they are associated with a unique set of organ-specific, immune-related adverse events. Among them, immune-related pneumonitis requires special attention because it is difficult to diagnose and potentially lethal. Accumulating real-world epidemiological data suggest that immune-related pneumonitis is more frequent than previously reported. Its diagnosis requires exclusion of other causes and assessment of radiographic features on high-resolution CT of the chest. Management of immune-related pneumonitis is based on the use of immunosuppressants. Future research should be focused on finding predictive biomarkers for immune-related pneumonitis as well as optimizing its management.

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“…Combination therapy of PD‐1/PD‐L1 and CTLA‐4 inhibitors carries a higher risk of pulmonary toxicity, with an incidence of 6.88% for all grade pneumonitis and 1.88% incidence for grade 3–4 58 . While validated risk factors for pulmonary are currently unknown, there is thought that characteristics such as sex, age, smoking history and baseline lung disease may predispose patients 59 . Studies have observed that patients with baseline interstitial lung disease have increased risk, as well as tumour type, such as lung and renal cell carcinoma, may lead to an increased incidence of pulmonary toxicity 60,61 .…”

Section: Introductionmentioning

confidence: 99%

Evolving insights into the mechanisms of toxicity associated with immune checkpoint inhibitor therapy

Mangan

McAlister

Balko

et al. 2020

Brit J Clinical Pharma

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Immune checkpoint inhibitors have emerged as a revolutionary treatment option for patients with various types of malignancy. Although these agents afford a significant improvement in outcomes for melanoma and other previously untreatable malignancies, their novel mechanism of action may predispose patients to immune‐related adverse effects (irAEs). In the tumour neoantigen environment, these irAEs are due to the activation of the immune system by the blockade of suppressive checkpoints, leading to increases in T‐cell activation and proliferation. IrAEs have been reported in almost any organ and at any point in time, even months to years after discontinuation of therapy. Certain populations with distinct physiological changes, genetic risk factors, and specific antigen exposures may be more highly predisposed to develop irAEs. This review discusses the incidence and mechanisms of irAEs and the relationship between host factors and irAE occurrence.

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Clinical diagnosis and treatment of immune checkpoint inhibitor‐associated pneumonitis

Cited by 67 publications

References 19 publications

Risk factors of immune checkpoint inhibitor-related interstitial lung disease in patients with lung cancer: a single-institution retrospective study

Risk factors of immune checkpoint inhibitor-related interstitial lung disease in patients with lung cancer: a single-institution retrospective study

Immune Checkpoint Inhibitor-Related Pneumonitis

Evolving insights into the mechanisms of toxicity associated with immune checkpoint inhibitor therapy

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