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Journal of Cancer Research and Clinical... Aug 2023As immune checkpoint inhibitors (ICIs) are widely used, a series of immune-related adverse events (irAEs) have been reported, including immune checkpoint... (Review)
Review
As immune checkpoint inhibitors (ICIs) are widely used, a series of immune-related adverse events (irAEs) have been reported, including immune checkpoint inhibitor-related pneumonitis (ICI-pneumonitis). The incidence of ICI-pneumonitis is higher in reality than in clinical trials. The diagnosis is challenging, mainly based on clinical and imaging features, and requires the exclusion of other causes. The data on the biological mechanisms of ICI-pneumonitis are scarce, resulting in little knowledge of the best treatment for ICI-pneumonitis. Bronchoalveolar lavage (BAL) may be helpful to identify the biological differences or find predictive biomarkers, and may in turn help to develop phenotype-specific targeted drugs to treat ICI-pneumonitis. Herein, we outline the characterization of immunomodulatory factors and cells in bronchoalveolar lavage fluid for ICI-pneumonitis. Through careful sorting and literature review, we find crosstalk between pathogenic Th17/Th1 cells (i.e., Th17.1) and pro-inflammatory monocytes, and activation of Th17(/Th1)/IL-17A (/IFN-γ) pathways may play a key role in the pathogenesis of ICI-pneumonitis. Disruption of the interaction between pathogenic Th17/Th1 cells and pro-inflammatory monocytes (such as, anti-IL-23) may be a potential treatment for ICI-pneumonitis. We first describe the possible pathophysiological mechanisms of ICI-pneumonitis, hoping to contribute to the optimization of diagnosis and treatment, as well as provide readers with research inspiration.
Topics: Humans; Immune Checkpoint Inhibitors; Bronchoalveolar Lavage Fluid; Pneumonia
PubMed: 36944820
DOI: 10.1007/s00432-023-04696-0 -
BMC Cancer Mar 2023With the application of immune checkpoint inhibitors (ICIs) in cancer treatment, more and more attention has been paid to checkpoint inhibitor-related pneumonitis (CIP),...
BACKGROUND
With the application of immune checkpoint inhibitors (ICIs) in cancer treatment, more and more attention has been paid to checkpoint inhibitor-related pneumonitis (CIP), which requires a better understanding of its clinical characteristics and therapeutic effects.
METHODS
The clinical and imaging data of 704 patients with non-small cell lung cancer (NSCLC) who received immunotherapy were analyzed retrospectively; the clinical characteristics of CIP were summarized, and the therapeutic regimens and effects of the patients were summarized.
RESULTS
36 CIP patients were included in the research. The most common clinical symptoms were cough, shortness of breath and fever. The CT manifestations were summarized as follows: Organizing pneumonia (OP) in 14 cases (38.9%), nonspecific interstitial pneumonia (NSIP) in 14 cases (38.9%), hypersensitiviy pneumonitis(HP) in 2 cases (6.3%), diffuse alveolar damage in 1 case (3.1%) and atypical imaging manifestations in 5 cases (13.9%). 35 cases received glucocorticoid therapy, 6 patients were treated with gamma globulin and 1 patient was treated with tocilizumab. There were no deaths in CIP G1-2 patients and 7 deaths occured in CIP G3-4 patients. 4 patients were treated again with ICIs.
CONCLUSION
We found that glucocorticoid 1-2 mg/kg was effective for most patients with moderate to severe CIP, and a few patients with hormone insensitivity needed early immunosuppressive therapy. A few patients can be rechallenged with ICIs, but CIP recurrence needs to be closely monitored.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Glucocorticoids; Lung Neoplasms; Retrospective Studies; Pneumonia
PubMed: 36869304
DOI: 10.1186/s12885-023-10649-0 -
Clinical Lung Cancer Sep 2020Approximately one third of patients with non-small-cell lung cancer (NSCLC) present with stage III or locally advanced NSCLC. These patients have historically been... (Review)
Review
Approximately one third of patients with non-small-cell lung cancer (NSCLC) present with stage III or locally advanced NSCLC. These patients have historically been managed with chemoradiotherapy. However, outcomes for these patients remain poor, with a 5-year survival rate between 15% and 32%. Immune checkpoint inhibitors have revolutionized the treatment of patients with NSCLC. One such agent, durvalumab, a selective high-affinity human immunoglobulin G1 monoclonal antibody that blocks programmed cell death ligand 1 binding to programmed cell death protein 1 and cluster of differentiation 80, was recently approved in the consolidation setting after completion of definitive platinum-based chemoradiotherapy and has become the current standard of care for patients with stage III locally advanced NSCLC. Immune checkpoint blockade is associated with increased risk of immunotherapy-related adverse events, which can be managed most effectively when detected early, ideally in the context of a multidisciplinary approach. Pneumonitis represents the potentially most severe and life-threatening of all reported immunotherapy-related adverse events, but it is further complicated in the context of recent prior therapies also known to cause pulmonary toxicity, such as radiotherapy. However, there are major gaps in our ability to identify immunotherapy-related pneumonitis and distinguish it from radiation pneumonitis. This review aims to define the key steps in the detection, diagnosis, and treatment of immunotherapy-related pneumonitis.
Topics: Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Humans; Immune Checkpoint Inhibitors; Lung Neoplasms; Pneumonia; Prognosis
PubMed: 32576443
DOI: 10.1016/j.cllc.2020.02.025 -
La Radiologia Medica Feb 2023To compare the radiological findings of immune checkpoint inhibitor-related pneumonitis (IRP) and COVID-19 pneumonia, evaluating the potential of the CO-RADS score to...
OBJECTIVES
To compare the radiological findings of immune checkpoint inhibitor-related pneumonitis (IRP) and COVID-19 pneumonia, evaluating the potential of the CO-RADS score to differentiate between them.
METHODS
Two readers blindly reviewed chest CTs from age- and sex-matched groups of 33 patients with IRP and 33 patients with COVID-19 pneumonia. Each examiner evaluated the presence of 13 CT features, semiquantitatively scored lung involvement, and assigned a CO-RADS score. Inter-reader reliability in the assessment of CT features and CO-RADS categories was evaluated with Cohen's κ. Distribution differences between groups were evaluated with the χ, Fisher's, and Mann-Whitney U tests.
RESULTS
Substantial or higher inter-reader reliability was found in CO-RADS assignments (κ = 0.664) and in the evaluation of CT features (κ ≥ 0.638), among which the sole feature found to significantly differentiate IRP from COVID-19 pneumonia was unilateral presentation (p < 0.001). Lung involvement semiquantitative scores and CO-RADS scores were significantly higher (p < 0.001) in COVID patients (median involvement score 4, IQR 4-6; median CO-RADS score 5, IQR 4-5) than in IRP patients (median involvement score 2.5, IQR 2-4; median CO-RADS score 3, IQR 3-4) but exploratory analysis of CO-RADS specificity revealed comparatively low values, ranging between 51.5% (Reader 1) and 54.6% (Reader 2).
CONCLUSIONS
CT features of IRP and COVID-19 pneumonia frequently overlap, save for the extent of lung involvement and bilaterality. In the current SARS-CoV-2 pandemic, the low specificity of the CO-RADS score for the differential diagnosis of COVID-19 pneumonia and IRP may prompt to reconsider the role of imaging in IRP work-up.
Topics: Humans; COVID-19; Immune Checkpoint Inhibitors; SARS-CoV-2; Reproducibility of Results; Tomography, X-Ray Computed; Pneumonia; Retrospective Studies
PubMed: 36680711
DOI: 10.1007/s11547-023-01598-6 -
Frontiers in Immunology 2023Checkpoint inhibitor-related pneumonitis (CIP) is a complication of immunotherapy for malignant tumors that severely limits the treatment cycles as well as endangers... (Review)
Review
Checkpoint inhibitor-related pneumonitis (CIP) is a complication of immunotherapy for malignant tumors that severely limits the treatment cycles as well as endangers patients' health. The chest CT imaging features or typing of CIP and the application of radiomics will contribute to the precise prevention, early diagnosis and instant treatment of CIP. This article reviews the advances in the CT features and the application of radiomics in CIP.
Topics: Humans; Neoplasms; Pneumonia; Immunotherapy; Tomography, X-Ray Computed
PubMed: 36756121
DOI: 10.3389/fimmu.2023.1082980 -
Journal of Thoracic Oncology : Official... Sep 2021
Topics: Humans; Immune Checkpoint Inhibitors; Lung Neoplasms; Pneumonia; Retrospective Studies
PubMed: 34425997
DOI: 10.1016/j.jtho.2021.06.001 -
Advances in Respiratory Medicine 2022Immune-checkpoint inhibitors (ICIs) have revolutionized treatment of solid malignancies, leading in some cases to durable responses. However, an unchecked immune... (Review)
Review
Immune-checkpoint inhibitors (ICIs) have revolutionized treatment of solid malignancies, leading in some cases to durable responses. However, an unchecked immune response might lead to mild to severe immune-related adverse events (irAEs). Pulmonary toxicity, though often referred to as Immune checkpoint inhibitor-related pneumonitis (ICI-pneumonitis), covers a broad and overlapping spectrum of pulmonary manifestations and has been described in < 10% of patients receiving ICI either alone or in combination. However, the actual numbers in real-world populations are high, and are likely to increase as the therapeutic indications for ICIs continue to expand to include other malignancies. Drug withdrawal is the mainstay of treatment for ICI-pneumonitis. However, a good number of patients with higher grades of toxicity may need corticosteroids. Patients with refractory disease need additional immunosuppressive agents. In this brief review, we succinctly discuss the incidence, risk factors, mechanisms, clinical and radiologic manifestations, diagnosis and summarize the current management strategies of ICI-pneumonitis.
Topics: Humans; Immune Checkpoint Inhibitors; Incidence; Lung; Neoplasms; Pneumonia; Risk Factors
PubMed: 35731114
DOI: 10.5603/ARM.84782 -
Journal of the American Medical... Mar 2020This is the second of 2 parts of a narrative review of nursing home-associated pneumonia (NHAP) that deals with etiology and treatment in the nursing home. In the 1980s... (Review)
Review
This is the second of 2 parts of a narrative review of nursing home-associated pneumonia (NHAP) that deals with etiology and treatment in the nursing home. In the 1980s and 1990s, the etiology of NHAP was considered to be similar to community-acquired pneumonia (CAP). This belief was reflected in CAP guidelines until 2005 when the designation healthcare-associated pneumonia or HCAP was introduced and nursing home residents were included in the HCAP category. Patients in the HCAP group were thought to be at high risk for pneumonia because of multidrug resistant organisms and required empiric broad-spectrum antibiotic therapy much like people with hospital-acquired infection. Subsequent studies of the etiology of NHAP using sophisticated diagnostic testing found limited evidence of resistant organisms such as methicillin-resistant Staphylococcus aureus or resistant gram-negative organisms or atypical organisms. In terms of management of NHAP in the nursing home there are several considerations that are discussed: hospitalization decision, initial oral or parenteral therapy, timing of switch to an oral regimen if parenteral therapy is initially prescribed, duration of therapy with an emphasis on shorter courses, and follow-up during therapy including the use of the "antibiotic time out" protocol. The oral and parenteral antibiotic regimens recommended for treatment of NHAP in this report are based on limited information because there are no randomized controlled trials to define the optimum regimen. In conclusion, most residents with pneumonia can be treated successfully in the nursing home. However, there is an urgent need for a specific NHAP diagnosis and treatment guideline that will give providers guidance in the management of this infection in the nursing home.
Topics: Anti-Bacterial Agents; Community-Acquired Infections; Cross Infection; Humans; Methicillin-Resistant Staphylococcus aureus; Nursing Homes; Pneumonia
PubMed: 32061505
DOI: 10.1016/j.jamda.2020.01.012 -
Frontiers in Immunology 2022Whilst survival benefits of thoracic radiotherapy (TRT) followed by immune checkpoint inhibitor (ICI) have been reported in patients with lung cancer, the potential high...
PURPOSE
Whilst 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 MATERIALS
From 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.
RESULTS
With 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 (=0.05), mean lung dose (MLD, =0.038), percent volume of lung receiving ≥5 Gy (V5, =0.012) and percent volume of lung receiving ≥20 Gy (V20, =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, =0.004).
CONCLUSIONS
Treatment-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.
Topics: Humans; Immune Checkpoint Inhibitors; Lung Neoplasms; Pneumonia; Radiation Pneumonitis; Retrospective Studies; Risk Factors
PubMed: 35795657
DOI: 10.3389/fimmu.2022.918787 -
Lung Cancer (Amsterdam, Netherlands) Apr 2022Immune-mediated adverse events (imAEs), including all-cause immune-mediated pneumonitis, were reported in approximately 25% of patients in the placebo-controlled, phase...
INTRODUCTION
Immune-mediated adverse events (imAEs), including all-cause immune-mediated pneumonitis, were reported in approximately 25% of patients in the placebo-controlled, phase III PACIFIC trial of durvalumab monotherapy (for up to 12 months) in patients with unresectable, stage III NSCLC and no disease progression after concurrent chemoradiotherapy; only 3.4% of patients experienced grade 3/4 imAEs. With broad application of the PACIFIC regimen (consolidation durvalumab after chemoradiotherapy), now standard-of-care in this setting, there is a need to better characterize the occurrence of imAEs with this regimen.
METHODS
We performed descriptive, post-hoc, exploratory analyses to characterize the occurrence of imAEs (pneumonitis and non-pneumonitis) in PACIFIC in terms of: incidence, severity, and timing; clinical management and outcomes; and associations between the occurrence of imAEs and (1) all-cause AEs and (2) baseline patient, disease, and treatment characteristics.
RESULTS
Any-grade immune-mediated pneumonitis (9.4%) and non-pneumonitis imAEs (10.7%) occurred infrequently and were more common with durvalumab versus placebo. Grade 3/4 immune-mediated pneumonitis (1.9%) and non-pneumonitis imAEs (1.7%) were uncommon with durvalumab, as were fatal imAEs (0.8%; all pneumonitis). The most common non-pneumonitis imAEs with durvalumab were thyroid disorders, dermatitis/rash, and diarrhea/colitis. Dermatitis/rash had the shortest time to onset (from durvalumab initiation), followed by pneumonitis; dermatitis/rash had the longest time to resolution, followed by thyroid disorders. Most patients with immune-mediated pneumonitis (78.4%) and non-pneumonitis imAEs (56.3%) had these events occur ≤ 3 months after initiating durvalumab. ImAEs were well managed with administration of systemic corticosteroids, administration of endocrine replacement therapy, and interruption/discontinuation of durvalumab. Time elapsed from completion of prior radiotherapy to trial randomization (<14 vs. ≥ 14 days) did not impact either incidence or severity of imAEs. Durvalumab had a manageable safety profile broadly irrespective of whether patients experienced imAEs.
CONCLUSION
The risk of imAEs should not deter use of the PACIFIC regimen in eligible patients, as these events are generally well managed through appropriate clinical intervention.
Topics: Antibodies, Monoclonal; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Dermatitis; Exanthema; Humans; Lung Neoplasms; Pneumonia
PubMed: 35245844
DOI: 10.1016/j.lungcan.2022.02.003