Dataset Information

Pretreatment Lung Function and Checkpoint Inhibitor Pneumonitis in NSCLC.

ABSTRACT:

Introduction

Checkpoint inhibitor pneumonitis (CIP) is a serious toxicity of anti-programmed death-(ligand) 1 immunotherapy. Whether pretreatment differences in pulmonary function exist in patients who develop CIP is unknown. We analyzed the pulmonary function tests (PFTs) of patients with NSCLC treated with immune checkpoint inhibitors (ICIs) to evaluate whether pretreatment lung function was associated with CIP development.

Methods

Patients were included if they completed greater than or equal to 1 PFT within 2 years preceding ICI initiation. CIP status (CIP+: developed CIP, CIP-: did not develop CIP) was determined clinically. Generalized estimating equation-based linear regression was used to evaluate the effects of time and CIP on lung function. Primary outcomes included the following: percent-predicted forced expiratory volume in 1 second (FEV1pp), percent-predicted forced vital capacity (FVCpp), and FEV1/FVC.

Results

A total of 43 patients (34 CIP-, 9 CIP+) with 79 PFTs (59 CIP-, 20 CIP+) were included. CIP+ patients had a 21.7% lower pretreatment FEV1pp compared with the CIP- group (95% confidence interval: -38.6 to -4.7). No statistically significant differences in FVCpp or FEV1/FVC were observed. The prevalence of obstructive lung disease was similar in both groups at 67% and 62% for the CIP+ and CIP- cohorts, as was the prevalence of current/former smoking at 100% and 93%, respectively.

Conclusions

Pretherapy differences in lung function were evident between patients who did and did not develop CIP, though the prevalence of obstructive lung disease was similar. Prospective studies are needed to validate these findings, inform potential risk factors for CIP, and investigate the effects of ICI treatment and CIP on pulmonary function in patients with NSCLC.

SUBMITTER: Reuss JE

PROVIDER: S-EPMC8552105 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pretreatment Lung Function and Checkpoint Inhibitor Pneumonitis in NSCLC.

Reuss Joshua E JE Brigham Emily E Psoter Kevin J KJ Voong Khinh Ranh KR Shankar Bairavi B Ettinger David S DS Marrone Kristen A KA Hann Christine L CL Levy Benjamin B Feliciano Josephine L JL Brahmer Julie R JR Feller-Kopman David D Lerner Andrew D AD Lee Hans H Yarmus Lonny L Hales Russell K RK D'Alessio Franco F Danoff Sonye K SK Forde Patrick M PM Suresh Karthik K Naidoo Jarushka J

JTO clinical and research reports 20210826 10

<h4>Introduction</h4>Checkpoint inhibitor pneumonitis (CIP) is a serious toxicity of anti-programmed death-(ligand) 1 immunotherapy. Whether pretreatment differences in pulmonary function exist in patients who develop CIP is unknown. We analyzed the pulmonary function tests (PFTs) of patients with NSCLC treated with immune checkpoint inhibitors (ICIs) to evaluate whether pretreatment lung function was associated with CIP development.<h4>Methods</h4>Patients were included if they completed greate ...[more]

PMID: 34746881

Similar Datasets

Project description:BACKGROUND:Pneumonitis from immune checkpoint inhibitors (ICI) is a potentially fatal immune-related adverse event (irAE) from antiprogrammed death 1/programmed death ligand 1 immunotherapy. Most cases of ICI pneumonitis improve or resolve with 4-6 weeks of corticosteroid therapy. Herein, we report the incidence, clinicopathological features and management of patients with non-small cell lung cancer (NSCLC) and melanoma who developed chronic ICI pneumonitis that warrants ?12 weeks of immunosuppression. METHODS:Patients with ICI pneumonitis were identified from institutional databases of ICI-treated patients with advanced melanoma and NSCLC between January 2011 and July 2018. ICI pneumonitis was defined as clinical/radiographic evidence of lung inflammation without alternative diagnoses, adjudicated by a multidisciplinary team. Chronic ICI pneumonitis was defined as pneumonitis that persists or worsens with steroid tapering, and necessitates ?12 weeks of immunosuppression, after ICI discontinuation. Serial chest CT was used to assess radiological features, and tumor response by Response EvaluationCriteria for Solid Tumors V.1.1. Bronchoalveolar lavage fluid (BALF) samples were assessed by cell differential. Lung biopsy samples were evaluated by H&E staining and multiplex immunofluorescence (mIF), where available. RESULTS:Among 299 patients, 44 developed ICI pneumonitis (NSCLC: 5/205; melanoma: 1/94), and of these, 6 experienced chronic ICI pneumonitis. The overall incidence of chronic ICI pneumonitis was thus 2%. Of those who developed chronic ICI pneumonitis: the majority had NSCLC (5/6), all sustained disease control from ICIs, and none had other concurrent irAEs. Timing of chronic ICI pneumonitis development was variable (range: 0-50 months), and occurred at a median of 12 months post ICI start. Recrudescence of ICI pneumonitis occurred at a median of 6 weeks after initial steroid start (range: 3-12 weeks), with all patients requiring steroid reintroduction when tapered to ?10 mg prednisone/equivalent. The median total duration of steroids was 37 weeks (range: 16-43+weeks). Re-emergence of radiographic ICI pneumonitis occurred in the same locations on chest CT, in most cases (5/6). All patients who developed chronic ICI pneumonitis had BALF lymphocytosis on cell differential and organising pneumonia on lung biopsy at initial ICI pneumonitis presentation, with persistent BALF lymphocytosis and brisk CD8+ infiltration on mIF at pneumonitis re-emergence during steroid taper. CONCLUSIONS:A subset of patients who develop pneumonitis from ICIs will develop chronic ICI pneumonitis, that warrants long-term immunosuppression of ?12 weeks, and has distinct clinicopathological features.

Project description:BackgroundImmune checkpoint inhibitors (ICIs) have led to dramatic improvements in survival a subset of patients with non-small cell lung cancer (NSCLC); however, they have been shown to cause life-threatening toxicity such as immune checkpoint inhibitor-related pneumonitis (CIP). Our previous studies have shown that chronic obstructive pulmonary disease (COPD) and circulating cytokines are associated with clinical outcomes in NSCLC patients receiving ICIs. However, the relationship between these factors and the development of CIP is unclear. In this study, we retrospectively assessed NSCLC patients receiving ICIs to identify CIP risk factors.MethodsThis retrospective cohort study reviewed medical records of NSCLC patients receiving ICIs targeting programmed cell death 1 (PD-1) or its ligand PD-L1 between March 2017 and December 2020 at Zhongshan Hospital Fudan University. CIP was diagnosed by the treating investigator. Clinical characteristics and baseline plasma cytokines were collected. Logistic regression was used to compare clinical characteristics and circulating cytokine levels between patients with and without CIP to identify CIP risk factors.ResultsOf 164 NSCLC patients who received ICIs, CIP developed in 20 cases (12.2%). The presence of COPD [odds ratio (OR), 7.194; 95% confidence interval (CI): 1.130 to 45.798; P=0.037] and PD-L1 expression of ≥50% (OR, 7.184; 95% CI: 1.154 to 44.721; P=0.035) were independently associated with a higher incidence of CIP, whereas a higher baseline level of interleukin-8 (IL-8) was associated with a lower incidence of CIP (OR, 0.758; 95% CI: 0.587 to 0.978; P=0.033). The independent risk factors from final multivariate analysis were incorporated into a nomogram to predict the incidence of CIP. The nomogram model receiver operating characteristic (ROC) curve had a good predictive accuracy of 0.883 (95% CI: 0.806 to 0.959).ConclusionsIncreased risk of CIP independently associated with history of COPD, tumor PD-L1 expression ≥50%, and low baseline IL-8 level. The nomogram may hold promise for CIP risk assessment in the administration of ICIs.

Project description:PurposeWhilst survival benefits of thoracic radiotherapy (TRT) followed by immune checkpoint inhibitor (ICI) have been reported in patients with lung cancer, the potential high risk of treatment-related pneumonitis remains a concern. Asians may be more sensitive to lung toxicity than other races. This retrospective study intended to provide a comprehensive pneumonitis profile of TRT followed by ICI and investigate the risk factors from a Chinese cohort of lung cancer.Methods and materialsFrom January 2016 to July 2021, 196 patients with lung cancer who received TRT prior to ICI were retrospectively analyzed. Treatment-related pneumonitis, including checkpoint inhibitor pneumonitis (CIP), radiation pneumonitis (RP), and radiation recall pneumonitis (RRP), were recorded and graded through medical records and chest computed tomography. Characteristics predictive of pneumonitis were assessed using logistic regression models, and the receiver operating characteristic analyses were performed to identify optimal cut points for quantitative variables.ResultsWith a median follow-up of 18 months, a total of 108 patients (55.1%) developed treatment-related pneumonitis during ICI therapy, with an incidence of 25.5% for grade 2 or higher (G2+) and 4.1% for G3+. The overall rates of CIP, RP and RRP were 8.2% (n=16), 46.9% (n=92) and 7.1% (n=14), respectively. With a total mortality rate of 1.5%, vast majority of the patients recovered from pneumonitis or remained stable. No patients died of RRP. Half of the patients with G2+ RP who withheld ICI therapy restarted ICI safely after resolution of RP. The history of chronic pulmonary diseases (P=0.05), mean lung dose (MLD, P=0.038), percent volume of lung receiving ≥5 Gy (V5, P=0.012) and percent volume of lung receiving ≥20 Gy (V20, P=0.030) predicted the occurrence of RRP in univariate analyses. Interval between TRT and ICI less than 3 months was an independent predictor for G2+ treatment-related pneumonitis in a multivariate model (Odds ratio OR=2.787, P=0.004).ConclusionsTreatment-related pneumonitis, especially RRP, is acceptable and manageable in the setting of TRT followed by ICI in this Asian population. Dosimetric parameters MLD, V5 and V20 may improve the predictions of RRP in clinical practice.

Project description:BackgroundImmune checkpoint inhibitors (ICIs) have become standard treatments for lung cancer patients. Immune checkpoint inhibitor-related pneumonitis (CIP) was the leading cause of death among ICIs-related adverse events (irAEs). Recurrent episodes of CIP without rechallenge of ICIs were reported in several cases and maybe a unique feature of CIP. Knowledge gaps remain regarding the rate and risk factors associated to CIP's recurrence.MethodsData from 1,102 lung cancer patients receiving ICIs treatment between January 2016 and January 2021 were retrospectively collected and analyzed. CIP was diagnosed according to typical clinical features and/or new typical imaging changes. Recurrence of CIP (CIP-R) was defined as recurrent CIP after initial CIP improved after proper treatment. Logistic regression was used to assess risk factors associated with CIP recurrence.ResultsEighty out of 1,102 (7.26%) patients were diagnosed with CIP. Twenty of those 78 (25.64%) patients suffered CIP-R, 2 patients died and were therefore excluded from the denominator. The median onset of initial pneumonitis for patients without and with recurrence was 3.49 months [interquartile range (IQR), 0.26-31.93 months] and 2.78 months (IQR, 1.22-20.93 months), respectively (P=0.48). The median interval duration between initial CIP and CIP-R was 1.54 months (IQR, 0.98-16.70 months). Recurrence of CIP was more common in males (P=0.03), squamous histology (P=0.016), and in patients who received chest radiotherapy (P=0.049). The duration of prednisolone equivalent dose ≥15 mg/day in CIP-R was significantly shorter, at 3.71 weeks (2.86-6.57 weeks) compared with 6.36 weeks in those without recurrence (IQR, 3.12-9.86 weeks) (P=0.001). Non-squamous histology [odds ratio (OR), 0.182; 95% confidence interval (CI): 0.038-0.860; P=0.031] and prolonged administration of prednisolone equivalent dose ≥15 mg/day for more than 4 weeks (OR, 0.082; 95% CI: 0.02-0.342; P=0.001) were independently associated with a decreased odds of CIP-R development.ConclusionsCIP-R in a real-world lung cancer cohort is not uncommon, both in patients with and without rechallenge of ICIs. A duration of prednisolone equivalent dose ≥15 mg/day of at least 4 weeks during the tapering process of corticosteroids were recommend in patients with CIP.

Project description:BackgroundPatients with non-small cell lung cancer may develop pneumonitis after thoracic radiotherapy (RT) and immune checkpoint inhibitors (ICIs). We hypothesized that distinct morphologic features are associated with different pneumonitis etiologies.Materials and methodsWe systematically compared computed tomography (CT) features of RT- versus ICI-pneumonitis. Clinical and imaging features were tested for association with pneumonitis severity. Lastly, we constructed an exploratory radiomics-based machine learning (ML) model to discern pneumonitis etiology.ResultsBetween 2009 and 2019, 82 patients developed pneumonitis: 29 after thoracic RT, 23 after ICI, and 30 after RT + ICI. Fifty patients had grade 2 pneumonitis, 22 grade 3, and 7 grade 4. ICI-pneumonitis was more likely bilateral (65% vs. 28%; p = .01) and involved more lobes (66% vs. 45% involving at least three lobes) and was less likely to have sharp border (17% vs. 59%; p = .004) compared with RT-pneumonitis. Pneumonitis morphology after RT + ICI was heterogeneous, with 47% bilateral, 37% involving at least three lobes, and 40% sharp borders. Among all patients, risk factors for severe pneumonitis included poor performance status, smoking history, worse lung function, and bilateral and multifocal involvement on CT. An ML model based on seven radiomic features alone could distinguish ICI- from RT-pneumonitis with an area under the receiver-operating curve of 0.76 and identified the predominant etiology after RT + ICI concordant with multidisciplinary consensus.ConclusionRT- and ICI-pneumonitis exhibit distinct spatial features on CT. Bilateral and multifocal lung involvement is associated with severe pneumonitis. Integrating these morphologic features in the clinical management of patients who develop pneumonitis after RT and ICIs may improve treatment decision-making.Implications for practicePatients with non-small cell lung cancer often receive thoracic radiation and immune checkpoint inhibitors (ICIs), both of which can cause pneumonitis. This study identified similarities and differences in pneumonitis morphology on computed tomography (CT) scans among pneumonitis due to radiotherapy (RT) alone, ICI alone, and the combination of both. Patients who have bilateral CT changes involving at least three lobes are more likely to have ICI-pneumonitis, whereas those with unilateral CT changes with sharp borders are more likely to have radiation pneumonitis. After RT and/or ICI, severe pneumonitis is associated with bilateral and multifocal CT changes. These results can help guide clinicians in triaging patients who develop pneumonitis after radiation and during ICI treatment.

Dataset Information

Pretreatment Lung Function and Checkpoint Inhibitor Pneumonitis in NSCLC.

Introduction

Methods

Results

Conclusions

Publications

Pretreatment Lung Function and Checkpoint Inhibitor Pneumonitis in NSCLC.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets