Immune checkpoint inhibitor‐associated interstitial lung diseases correlate with better prognosis in patients with advanced non‐small‐cell lung cancer

Sugano, Teppei; Seike, Masahiro; Saito, Yoshinobu; Kashiwada, Takeru; Terasaki, Yasuhiro; Takano, Natsuki; Hisakane, Kakeru; Takahashi, Satoshi; Tanaka, Toru; Takeuchi, Susumu; Miyanaga, Akihiko; Minegishi, Yuji; Noro, Rintaro; Kubota, Keiichi; Gemma, Akihiko

doi:10.1111/1759-7714.13364

Cited by 42 publications

(38 citation statements)

References 26 publications

(61 reference statements)

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“…Similarly, BAL CD8+ cells and TILs from this patient exhibited the same expression pattern of PD1 and T-cell immunoglobulin mucin-3 receptor which differed from that of BAL CD8+ cells found in bacterial or chemotherapy-induced pneumonitis [14]. Therefore, BAL findings may also explain the occurrence of CIP in cancers that respond to PD1 inhibitors as we observed in our patients and has been broadly reported [9,15].…”

Section: Discussionsupporting

confidence: 80%

Cellular Analysis of Bronchoalveolar Lavage Fluid to Narrow Differential Diagnosis of Checkpoint Inhibitor-related Pneumonitis in Metastatic Melanoma

Strippoli

Fucci

Negri

et al. 2020

Preprint

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Background: The diagnosis of check-point inhibitor-related pneumonitis (CIP) relies on radiological and clinical patterns which are not specific and can mimic other conditions (cancer progression, infectious diseases or interstitial pneumonitis). Cell pattern analysis of bronchoalveolar lavage (BAL) is well-known to support the diagnosis of interstitial lung disease; nevertheless, this analysis is somewhat performed and not required by immune-toxicity management guidelines for CIP. Methods: We performed BAL analysis in 5 metastatic melanoma (MM) patients who developed CIP among 112 patients treated with checkpoint inhibitors. We also correlated the BAL features with the computed tomography (CT) scan patterns and with various peripheral blood parameters to better define the profile of this patient population. Results: BAL flow cytometer and cytopathology analyses showed typical and homogeneous features with increased lymphoid population, prevalent CD8+ T cells and inversion of the CD4/CD8 ratio . Moreover, the extent of activated CD3+HLA-DR+ T cells was related to the grading of adverse events. Blood leucocytosis, hypoxemia, normal values for procalcitonin and lactate dehydrogenase were also found together with a cryptogenic organizing pneumonia-like radiologic pattern. In all our patients, CIP was associated with partial or complete response. Conclusions: Identification of a specific BAL cellular pattern allows clinicians to place this investigation in the appropriate position of CIP diagnosis and management to avoid misdiagnosis or considering this condition as progressive disease and delaying proper treatment.

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Section: Discussionsupporting

confidence: 80%

Cellular Analysis of Bronchoalveolar Lavage Fluid to Narrow Differential Diagnosis of Checkpoint Inhibitor-related Pneumonitis in Metastatic Melanoma

Strippoli

Fucci

Negri

et al. 2020

Preprint

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“…Thus, severe ICI-ILD may not be a predictive marker of overall survival prolongation in patients with lung cancer. Previous studies have reported the prognostic effect of ICI-ILD, but it is still controversial 11,12 . A recent prospective study reported that ICI-ILD had no effect on prognosis 11 .…”

Section: Discussionmentioning

confidence: 99%

“…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 . Therefore, ICI-ILD onset is a limiting factor to continue or not continue ICI treatment and to achieve treatment benefits in patients with lung cancer.…”

Section: Introductionmentioning

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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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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“…A French multi-center retrospective study showed that 3.5% of all patients treated with ICIs developed ICIrelated ILD (ICI-ILD). 14 However, it is more common in patients with lung cancer who are treated with ICIs, with the prevalence reported as 36.8%, 15 13.2%, 16 and 12% 17 in three recent studies. The occurrence of ICI-ILD is more common in males with a history of smoking 14 and is highly associated with pre-existing interstitial lung disease.…”

Section: Discussionmentioning

confidence: 99%

“…The occurrence of ICI-ILD is more common in males with a history of smoking 14 and is highly associated with pre-existing interstitial lung disease. 16,17 ICI-ILD often occurs earlier in lung cancer, with a median of 2.1 months after ICI treatments, 1 and presents as several radiologic patterns. 18 A total of 70-80% of ICI-ILD cases can be controlled through the prompt initiation of a high dose of steroids.…”

Section: Discussionmentioning

confidence: 99%

<p>Immune Checkpoint Inhibitor Therapy Achieved Complete Response for Drug-Sensitive<em> EGFR/ALK</em> Mutation-Negative Metastatic Pulmonary Large-Cell Neuroendocrine Carcinoma with High Tumor Mutation Burden: A Case Report</p>

Zhang¹,

Sun²,

Miao³

et al. 2020

OTT

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Large-cell neuroendocrine lung carcinoma (LCNELC) is classified into lung neuroendocrine tumors according to WHO 2015 classification guidelines and represents approximately 3% of all lung cancer. Because of the rarity of LCNELC, there is a lack of prospective studies guiding treatment. Here, we report a case of a patient with pT2aN2M0 stage IIIA LCNELC (drug-sensitive EGFR/ALK mutation-negative, PD-L1-negative but tumor mutation burden (TMB) high), who progressed rapidly after surgery but achieved a complete response to subsequent immune checkpoint inhibitor (ICI) therapy. The concentration of circulating tumor DNA (ctDNA) following the treatment course strongly reflects the response to ICI therapy. This report highlights the efficacy of ICI treatment in metastatic LCNELC patients with a high TMB and suggests that ctDNA analysis in detecting molecular residual disease may facilitate the personalization of ICI therapy.

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Immune checkpoint inhibitor‐associated interstitial lung diseases correlate with better prognosis in patients with advanced non‐small‐cell lung cancer

Cited by 42 publications

References 26 publications

Cellular Analysis of Bronchoalveolar Lavage Fluid to Narrow Differential Diagnosis of Checkpoint Inhibitor-related Pneumonitis in Metastatic Melanoma

Cellular Analysis of Bronchoalveolar Lavage Fluid to Narrow Differential Diagnosis of Checkpoint Inhibitor-related Pneumonitis in Metastatic Melanoma

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

<p>Immune Checkpoint Inhibitor Therapy Achieved Complete Response for Drug-Sensitive<em> EGFR/ALK</em> Mutation-Negative Metastatic Pulmonary Large-Cell Neuroendocrine Carcinoma with High Tumor Mutation Burden: A Case Report</p>

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