Dataset Information

Association of Preexisting Interstitial Lung Abnormalities With Immune Checkpoint Inhibitor-Induced Interstitial Lung Disease Among Patients With Nonlung Cancers.

ABSTRACT: Importance:Immune checkpoint inhibitor-induced interstitial lung disease (ICI-ILD) is clinically serious and life-threatening. Preexisting interstitial lung abnormalities have been shown to be risk factors for ICI-ILD in patients with lung cancer. Objective:To evaluate whether interstitial lung abnormalities are associated with ICI-ILD in patients with nonlung cancers. Design, Setting, and Participants:This cohort study was conducted between December 2015 and May 2019 at Hiroshima University Hospital. A total of 199 consecutive patients with head and neck cancer, malignant melanoma, oral cavity cancer, urological cancer, and gastrointestinal cancer who received anti-programmed cell death 1 (PD-1) antibody monotherapy were included. Data analysis was conducted from December 2015 to May 2019. Main Outcomes and Measures:The associations between potential risk factors and the development of ICI-ILD were examined. Information on patient characteristics before antibody administration, including chest computed tomography findings, was obtained. The diagnosis of ICI-ILD was defined as abnormal computed tomography shadows occurring during treatment with anti-PD-1 antibodies. Results:A total of 199 patients were enrolled in the study. The median (range) age was 66 (20-93) years, and most patients (133 [66.8%]) were men. Nineteen patients (9.5%) developed ICI-ILD. There was no significant difference in the baseline characteristics between patients with and without ICI-ILD. The logistic regression analyses revealed that interstitial lung abnormalities were associated with increased risk of ICI-ILD (odds ratio, 6.29; 95% CI, 2.34-16.92; P?

SUBMITTER: Shimoji K

PROVIDER: S-EPMC7662135 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Association of Preexisting Interstitial Lung Abnormalities With Immune Checkpoint Inhibitor-Induced Interstitial Lung Disease Among Patients With Nonlung Cancers.

Shimoji Kiyofumi K Masuda Takeshi T Yamaguchi Kakuhiro K Sakamoto Shinjiro S Horimasu Yasushi Y Nakashima Taku T Miyamoto Shintaro S Iwamoto Hiroshi H Fujitaka Kazunori K Hamada Hironobu H Takeno Sachio S Hide Michihiro M Teishima Jun J Ohdan Hideki H Hattori Noboru N

JAMA network open 20201102 11

<h4>Importance</h4>Immune checkpoint inhibitor-induced interstitial lung disease (ICI-ILD) is clinically serious and life-threatening. Preexisting interstitial lung abnormalities have been shown to be risk factors for ICI-ILD in patients with lung cancer.<h4>Objective</h4>To evaluate whether interstitial lung abnormalities are associated with ICI-ILD in patients with nonlung cancers.<h4>Design, setting, and participants</h4>This cohort study was conducted between December 2015 and May 2019 at Hi ...[more]

PMID: 33180128

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Project description:Interstitial lung abnormalities have been associated with lower 6-minute walk distance, diffusion capacity for carbon monoxide, and total lung capacity. However, to our knowledge, an association with mortality has not been previously investigated.To investigate whether interstitial lung abnormalities are associated with increased mortality.Prospective cohort studies of 2633 participants from the FHS (Framingham Heart Study; computed tomographic [CT] scans obtained September 2008-March 2011), 5320 from the AGES-Reykjavik Study (Age Gene/Environment Susceptibility; recruited January 2002-February 2006), 2068 from the COPDGene Study (Chronic Obstructive Pulmonary Disease; recruited November 2007-April 2010), and 1670 from ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints; between December 2005-December 2006).Interstitial lung abnormality status as determined by chest CT evaluation.All-cause mortality over an approximate 3- to 9-year median follow-up time. Cause-of-death information was also examined in the AGES-Reykjavik cohort.Interstitial lung abnormalities were present in 177 (7%) of the 2633 participants from FHS, 378 (7%) of 5320 from AGES-Reykjavik, 156 (8%) of 2068 from COPDGene, and in 157 (9%) of 1670 from ECLIPSE. Over median follow-up times of approximately 3 to 9 years, there were more deaths (and a greater absolute rate of mortality) among participants with interstitial lung abnormalities when compared with those who did not have interstitial lung abnormalities in the following cohorts: 7% vs 1% in FHS (6% difference [95% CI, 2% to 10%]), 56% vs 33% in AGES-Reykjavik (23% difference [95% CI, 18% to 28%]), and 11% vs 5% in ECLIPSE (6% difference [95% CI, 1% to 11%]). After adjustment for covariates, interstitial lung abnormalities were associated with a higher risk of death in the FHS (hazard ratio [HR], 2.7 [95% CI, 1.1 to 6.5]; P?=?.03), AGES-Reykjavik (HR, 1.3 [95% CI, 1.2 to 1.4]; P?<?.001), COPDGene (HR, 1.8 [95% CI, 1.1 to 2.8]; P?=?.01), and ECLIPSE (HR, 1.4 [95% CI, 1.1 to 2.0]; P?=?.02) cohorts. In the AGES-Reykjavik cohort, the higher rate of mortality could be explained by a higher rate of death due to respiratory disease, specifically pulmonary fibrosis.In 4 separate research cohorts, interstitial lung abnormalities were associated with a greater risk of all-cause mortality. The clinical implications of this association require further investigation.

Project description:ImportanceDerived neutrophils/(leukocytes minus neutrophils) ratio (dNLR) and lactate dehydrogenase (LDH) level have been correlated with immune checkpoint inhibitor (ICI) outcomes in patients with melanoma.ObjectiveTo determine whether pretreatment dNLR and LDH are associated with resistance to ICIs in patients with advanced non-small cell lung cancer (NSCLC).Design, setting, and participantsMulticenter retrospective study with a test (n = 161) and a validation set (n = 305) treated with programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors in 8 European centers, and a control cohort (n = 162) treated with chemotherapy only. Complete blood cell counts, LDH, and albumin levels were measured before ICI treatment. A lung immune prognostic index (LIPI) based on dNLR greater than 3 and LDH greater than upper limit of normal (ULN) was developed, characterizing 3 groups (good, 0 factors; intermediate, 1 factor; poor, 2 factors).Main outcomes and measuresThe primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS) and disease control rate (DCR).ResultsIn the pooled ICI cohort (N = 466), 301 patients (65%) were male, 422 (90%) were current or former smokers, and 401 (87%) had performance status of 1 or less; median age at diagnosis was 62 (range, 29-86) years; 270 (58%) had adenocarcinoma and 159 (34%) had squamous histologic subtype. Among 129 patients with PD-L1 data, 96 (74%) had PD-L1 of at least 1% by immunohistochemical analysis, and 33 (26%) had negative results. In the test cohort, median PFS and OS were 3 (95% CI, 2-4) and 10 (95% CI, 8-13) months, respectively. A dNLR greater than 3 and LDH greater than ULN were independently associated with OS (hazard ratio [HR] 2.22; 95% CI, 1.23-4.01 and HR, 2.51; 95% CI, 1.32-4.76, respectively). Median OS for poor, intermediate, and good LIPI was 3 months (95% CI, 1 month to not reached [NR]), 10 months (95% CI, 8 months to NR), and 34 months (95% CI, 17 months to NR), respectively, and median PFS was 2.0 (95% CI, 1.7-4.0), 3.7 (95% CI, 3.0-4.8), and 6.3 (95% CI, 5.0-8.0) months (both P < .001). Disease control rate was also correlated with dNLR greater than 3 and LDH greater than ULN. Results were reproducible in the ICI validation cohort for OS, PFS, and DCR, but were nonsignificant in the chemotherapy cohort.Conclusions and relevancePretreatment LIPI, combining dNLR greater than 3 and LDH greater than ULN, was correlated with worse outcomes for ICI, but not for chemotherapy, suggesting that LIPI can serve as a potentially useful tool when selecting ICI treatment, raising the hypothesis that the LIPI might be useful for identifying patients unlikely to benefit from treatment with an ICI.

Dataset Information

Association of Preexisting Interstitial Lung Abnormalities With Immune Checkpoint Inhibitor-Induced Interstitial Lung Disease Among Patients With Nonlung Cancers.

Publications

Association of Preexisting Interstitial Lung Abnormalities With Immune Checkpoint Inhibitor-Induced Interstitial Lung Disease Among Patients With Nonlung Cancers.

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