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The Oncologist Nov 2023Immune checkpoint inhibitor (ICI) pneumonitis causes substantial morbidity and mortality. Estimates of real-world incidence and reported risk factors vary substantially.
INTRODUCTION
Immune checkpoint inhibitor (ICI) pneumonitis causes substantial morbidity and mortality. Estimates of real-world incidence and reported risk factors vary substantially.
METHODS
We conducted a retrospective review of 419 patients with advanced non-small cell lung cancer (NSCLC) who were treated with anti-PD-(L)1 with or without anti-CTLA-4 therapy. Clinical, imaging, and microbiological data were evaluated by multidisciplinary adjudication teams. The primary outcome of interest was grade ≥2 (CTCAEv5) pneumonitis. Clinicopathologic variables, tobacco use, cancer therapies, and preexisting lung disease were assessed for univariate effects using Cox proportional hazards models. We created multivariate Cox proportional hazards models to assess risk factors for pneumonitis and mortality. Pneumonitis, pneumonia, and progression were modeled as time-dependent variables in mortality models.
RESULTS
We evaluated 419 patients between 2013 and 2021. The cumulative incidence of pneumonitis was 9.5% (40/419). In a multivariate model, pneumonitis increased the risk for mortality (HR 1.6, 95% CI, 1.0-2.5), after adjustment for disease progression (HR 1.6, 95% CI, 1.4-1.8) and baseline shortness of breath (HR 1.5, 95% CI, 1.2-2.0). Incomplete resolution was more common with more severe pneumonitis. Interstitial lung disease was associated with higher risk for pneumonitis (HR 5.4, 95% CI, 1.1-26.6), particularly in never smokers (HR 26.9, 95% CI, 2.8-259.0).
CONCLUSION
Pneumonitis occurred at a high rate and significantly increased mortality. Interstitial lung disease, particularly in never smokers, increased the risk for pneumonitis.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Incidence; Lung Neoplasms; Pneumonia; Risk Factors; Lung Diseases, Interstitial; Retrospective Studies
PubMed: 37156009
DOI: 10.1093/oncolo/oyad118 -
Expert Opinion on Biological Therapy Sep 2020The COVID-19 pandemic occurred amid the cancer immunotherapy revolution. Immune checkpoint inhibitors (ICIs) have become the standard of care for several solid cancers...
INTRODUCTION
The COVID-19 pandemic occurred amid the cancer immunotherapy revolution. Immune checkpoint inhibitors (ICIs) have become the standard of care for several solid cancers and are associated with peculiar toxicities, including pneumonitis which has similar features to COVID-19 pneumonia.
AREAS COVERED
We summarize the main hallmarks of lung injury induced by ICIs and severe acute respiratory syndrome coronavirus 2 and discuss the critical aspects for differential diagnosis and management. Symptoms and radiological findings are often similar; conversely, treatments are quite different. Furthermore, we focus on potential interactions generating hypotheses that need confirmatory studies.
EXPERT OPINION
All cancer patients treated with immunotherapy should receive screening for SARS-CoV-2. This would improve the diagnosis and management of pneumonia and guide therapeutic choices. Furthermore, clinicians could estimate the risk/benefit of continuing ICI treatment in COVID-19 positive patients. Temporary withdrawal of the immunotherapy treatment pending resolution of viral infection may be a reasonable option in long-responders patients.
Topics: Betacoronavirus; COVID-19; Coronavirus Infections; Diagnosis, Differential; Disease Management; Humans; Immunotherapy; Neoplasms; Pandemics; Pneumonia, Viral; SARS-CoV-2
PubMed: 32588674
DOI: 10.1080/14712598.2020.1789097 -
BMJ Case Reports Jul 2021Pembrolizumab is a selective anti-PD-L1 humanised monoclonal antibody approved by the Food and Drug Administration for treating multiple cancers, including cervical...
Pembrolizumab is a selective anti-PD-L1 humanised monoclonal antibody approved by the Food and Drug Administration for treating multiple cancers, including cervical cancer, non-small cell lung cancer (NSCLC), renal cell carcinoma, bladder cancer, and squamous head and neck cancer. Pneumonitis is a rare but known complication of pembrolizumab treatment for NSCLC. The median time frame of its appearance is 2.8 months. However, we present a case of pneumonitis appearing within 48 hours. The patient presented with rapidly progressive respiratory failure, and imaging demonstrated diffuse bilateral patchy involvement of the upper lung lobe and pre-hilar regions, which likely indicate pneumonitis. Because of likely grade 3 pneumonitis, he was treated with steroids and showed immediate improvement of symptoms. Repeated CT imaging showed resolution of bilateral patchy infiltrates. He was discharged to the rehabilitation unit. Rapid recognition of pneumonitis as a side effect of pembrolizumab is important because early treatment can help prevent respiratory failure and possible death.
Topics: Antibodies, Monoclonal, Humanized; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Male; Pneumonia
PubMed: 34266820
DOI: 10.1136/bcr-2021-242493 -
Ugeskrift For Laeger May 2021In this review, we discuss viral pneumonias in an overall setting. Viruses are involved in about a quarter of all pneumonias, but despite literature in the past couple... (Review)
Review
In this review, we discuss viral pneumonias in an overall setting. Viruses are involved in about a quarter of all pneumonias, but despite literature in the past couple of decades emphasising this, the clinical effect remains elusive, and almost all hospitalised patients with pneumonia are treated with antibiotics. Thus, improved diagnostic methods and further research on the subject have the potential to benefit the overall treatment of patients with pneumonia, decrease antibiotic overconsumption and accelerate development of new antiviral therapeutics.
Topics: Adult; Anti-Bacterial Agents; Antiviral Agents; Humans; Pneumonia; Pneumonia, Viral
PubMed: 33998441
DOI: No ID Found -
Journal of the American Veterinary... Jul 2019
Topics: Animals; Cat Diseases; Cats; Female; Pneumonia
PubMed: 31194663
DOI: 10.2460/javma.255.1.63 -
Indian Pediatrics Nov 2021An eight month old boy presented with a subacute febrile illness and radiological evidence of multifocal cavitatory consolidations in the lungs. He continued to worsen...
An eight month old boy presented with a subacute febrile illness and radiological evidence of multifocal cavitatory consolidations in the lungs. He continued to worsen despite multiple oral and intravenous antibiotics. Preterminally, he developed respiratory distress, hepatosplenomegaly, bicytopenia, and hepatic dysfunction. Investigation for cause of persistent pneumonia resulted in a diagnosis of chronic granulomatous disease on the basis of Dihydrorhodamine assay and genetic analysis. Postmortem blood culture grew Burkholderia cenocepacia. Autopsy revealed necrotizing granulomatous inflammation with massive necrosis and abscesses in bilateral lungs. No organism could be identified by traditional stains on autopsy. Conventional PCR targeting 16S ribosomal DNA yielded Nocardia pseudobrasiliensis. In conclusion, an unusual course of pneumonia warrants invasive investigations for isolation of underlying organism, which not only provides guidance to choice of antimicrobials but also provides clue to an underlying disease.
Topics: Abscess; Anti-Bacterial Agents; Autopsy; Granulomatous Disease, Chronic; Humans; Infant; Male; Pneumonia
PubMed: 34837368
DOI: No ID Found -
Frontiers in Immunology 2023Immune checkpoint inhibitors (ICI) may cause pneumonitis, resulting in potentially fatal lung inflammation. However, distinguishing pneumonitis from pneumonia is...
Heterogenous lung inflammation CT patterns distinguish pneumonia and immune checkpoint inhibitor pneumonitis and complement blood biomarkers in acute myeloid leukemia: proof of concept.
BACKGROUND
Immune checkpoint inhibitors (ICI) may cause pneumonitis, resulting in potentially fatal lung inflammation. However, distinguishing pneumonitis from pneumonia is time-consuming and challenging. To fill this gap, we build an image-based tool, and further evaluate it clinically alongside relevant blood biomarkers.
MATERIALS AND METHODS
We studied CT images from 97 patients with pneumonia and 29 patients with pneumonitis from acute myeloid leukemia treated with ICIs. We developed a CT-derived signature using a habitat imaging algorithm, whereby infected lungs are segregated into clusters ("habitats"). We validated the model and compared it with a clinical-blood model to determine whether imaging can add diagnostic value.
RESULTS
Habitat imaging revealed intrinsic lung inflammation patterns by identifying 5 distinct subregions, correlating to lung parenchyma, consolidation, heterogenous ground-glass opacity (GGO), and GGO-consolidation transition. Consequently, our proposed habitat model (accuracy of 79%, sensitivity of 48%, and specificity of 88%) outperformed the clinical-blood model (accuracy of 68%, sensitivity of 14%, and specificity of 85%) for classifying pneumonia versus pneumonitis. Integrating imaging and blood achieved the optimal performance (accuracy of 81%, sensitivity of 52% and specificity of 90%). Using this imaging-blood composite model, the post-test probability for detecting pneumonitis increased from 23% to 61%, significantly ( = 1.5 - 9) higher than the clinical and blood model (post-test probability of 22%).
CONCLUSION
Habitat imaging represents a step forward in the image-based detection of pneumonia and pneumonitis, which can complement known blood biomarkers. Further work is needed to validate and fine tune this imaging-blood composite model and further improve its sensitivity to detect pneumonitis.
Topics: Humans; Immune Checkpoint Inhibitors; Pneumonia; Tomography, X-Ray Computed; Inflammation; Biomarkers; Leukemia, Myeloid, Acute
PubMed: 37841255
DOI: 10.3389/fimmu.2023.1249511 -
Journal of the American College of... Apr 2021
Topics: Heart Failure; Humans; Pneumonia
PubMed: 33888246
DOI: 10.1016/j.jacc.2021.03.010 -
RoFo : Fortschritte Auf Dem Gebiete Der... Sep 2019
Topics: Acute Disease; Child; Community-Acquired Infections; Cross Infection; Diagnosis, Differential; Humans; Pneumonia; Pneumonia, Aspiration; Pneumonia, Bacterial; Pneumonia, Viral; Prognosis; Risk Factors
PubMed: 31430770
DOI: 10.1055/a-0943-0945 -
Journal For Immunotherapy of Cancer Apr 2021The clinically indistinguishable overlap between pneumonitis caused due to immune checkpoint inhibition (ICI) and pneumonia associated with COVID-19 has posed...
The clinically indistinguishable overlap between pneumonitis caused due to immune checkpoint inhibition (ICI) and pneumonia associated with COVID-19 has posed considerable challenges for patients with cancer and oncologists alike. The cancer community continues to face the challenges that lay at the complex immunological intersection of immune-based cancer therapy and immune dysregulation that results from COVID-19. Is there compounded immune dysregulation that could lead to poor outcomes? Could ICIs, in fact, ameliorate SARS-CoV-2-driven T-cell exhaustion?A little more is known about the kinetics of the viral replication in immunocompromised patients now as compared with earlier during the pandemic. Working knowledge of the diagnostic and therapeutic nuances of SARS-CoV-2 infection in patients with active cancers, issues related to viability and replication potential of the virus, unclear role of corticosteroids among those with diminished or dysfunctional effector T-cell repertoire, and the type of immunotherapy with differential risk of pneumonitis will inform decision making related to immunotherapy choices and decision for ICI continuation in the era of COVID-19.
Topics: Antineoplastic Agents, Immunological; COVID-19; COVID-19 Vaccines; Diagnosis, Differential; Humans; Immune Checkpoint Inhibitors; Immunocompromised Host; Immunotherapy; Neoplasms; Pneumonia; SARS-CoV-2; T-Lymphocytes
PubMed: 33931473
DOI: 10.1136/jitc-2020-002307