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Immunotherapy Oct 2023Immune checkpoint inhibitor (ICI)-related chronic pneumonitis is rare. Limited information is available on the characteristics of this condition. Herein, we present the... (Review)
Review
Immune checkpoint inhibitor (ICI)-related chronic pneumonitis is rare. Limited information is available on the characteristics of this condition. Herein, we present the case of a 54-year-old man with recurrent severe ICI-related pneumonitis. The patient developed fever and dyspnea during both episodes of pneumonitis. He had been previously diagnosed with gastric signet ring cell carcinoma and was undergoing treatment with an anti-PD-1 combination chemotherapy regimen. We reviewed previous case reports of ICI-related pneumonitis according to the primary cancer, time of onset in relation to ICI therapy and chest imaging findings. ICI-related pneumonitis can progress to chronic pneumonitis. Repeated computed tomography imaging showing lung changes in the same location may help to make the diagnosis.
Topics: Male; Humans; Middle Aged; Immune Checkpoint Inhibitors; Pneumonia; Lung; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms
PubMed: 37431609
DOI: 10.2217/imt-2023-0006 -
Respiration; International Review of... 2022Immune checkpoint inhibitors (ICIs) can lead to one of the common and quite serious immune-related adverse events (irAEs) in a real-world setting, namely, checkpoint... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Immune checkpoint inhibitors (ICIs) can lead to one of the common and quite serious immune-related adverse events (irAEs) in a real-world setting, namely, checkpoint inhibitor pneumonitis (CIP).
OBJECTIVE
We aimed to investigate the potential risk factors for CIP in cancer patients treated by ICIs and quantify the association.
METHODS
We conducted a systematic literature review in PubMed, EMBASE, and Web of Science from January 1, 2000, to March 20, 2022, with no study design restrictions. Studies evaluating the risk factors for CIP in cancer patients treated with ICIs-containing regimes were included. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for risk factors of CIP by using random-effect model. Heterogeneity was assessed by sensitivity analysis and subgroup analysis regarding CIP severity, geographical regions, cancer types, treatment regimes, and ICI types.
RESULTS
A total of 35 studies comprising 142,703 patients were eventually included. The incidence of grade I-V and grade III-V CIP in cancer patients was 0.16 (95% CI: 0.14-0.18) and 0.06 (95% CI: 0.05-0.08), respectively. When combining the adjusted ORs, the following risk factors were significantly associated with the development of CIP: squamous cell carcinoma (OR: 1.31, 95% CI: 1.18-1.45), previous thoracic radiotherapy (OR: 2.07, 95% CI: 1.34-3.19), preexisting radiation-induced pneumonitis (OR: 3.62, 95% CI: 1.53-8.58), preexisting respiratory disease (OR: 2.43, 95% CI: 1.45-4.07), preexisting interstitial lung disease (OR: 5.78, 95% CI: 3.08-10.85), preexisting ground glass attenuation (OR: 11.48, 95% CI: 1.13-116.74), preexisting honeycombing (OR: 6.11, 95% CI: 2.37-15.79), preexisting pulmonary emphysema (OR: 2.72, 95% CI: 1.00-7.36), use of pembrolizumab (OR: 2.89, 95% CI: 1.56-5.35, I2 = 0%), high PD-L1 expression (OR: 3.59, 95% CI: 1.23-10.50), and hypoalbuminemia (OR: 0.3, 95% CI: 0.14-0.64). When including the crude ORs, smoking history (OR: 1.39, 95% CI: 1.14-1.71), neutrophil-lymphocyte ratio (OR: 1.04, 95% CI: 1.01-1.08), and c-reactive protein (OR: 1.08, 95% CI: 1.01-1.16) were also risk factors for CIP.
CONCLUSION
Histological characteristics, specific previous lung diseases and treatment history, treatment regimen, PD-L1 expression level, and serological biomarkers are all closely associated with the development of CIP. These findings would be useful for oncologists to optimize the appropriate options of ICIs and close monitoring during immunotherapy treatments, particularly for patients identified as having a higher risk for CIP.
Topics: Humans; Antineoplastic Agents, Immunological; B7-H1 Antigen; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Immunotherapy; Lung Neoplasms; Pneumonia; Risk Factors
PubMed: 36108598
DOI: 10.1159/000526141 -
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 -
Expert Opinion on Drug Safety May 2021: The development of immune checkpoint inhibitors (ICIs) has been a breakthrough in the treatment of several types of cancer. With the widespread use of ICIs in clinical... (Review)
Review
: The development of immune checkpoint inhibitors (ICIs) has been a breakthrough in the treatment of several types of cancer. With the widespread use of ICIs in clinical practice, checkpoint inhibitor pneumonitis (CIP) is expected to increase and its management will pose a challenge for clinicians.: In this article, we review the incidence, associated risk factors, radiological patterns, clinical features, and management of CIP.: Several clinical trials assessing the efficacy and safety of combination treatments with various drugs and ICIs have been conducted. From the results of these trials, CIP is thought to be an acceptable side effect because the frequency of its development was slightly higher during combination therapies than during ICI monotherapies. However, the risk of developing CIP associated with combinations of chemotherapy and ICIs may be higher in the real world than in clinical trials. Because combinations of chemotherapy and ICIs are associated with increased toxicity, the proper management of immune-related adverse events is necessary to maximize the efficacy of the treatment.
Topics: Antineoplastic Combined Chemotherapy Protocols; Humans; Immune Checkpoint Inhibitors; Incidence; Neoplasms; Pneumonia; Risk Factors
PubMed: 33650443
DOI: 10.1080/14740338.2021.1898584 -
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 -
Current Opinion in Infectious Diseases Apr 2021This review aims to evaluate the evidence and recommendations for the prescription of corticosteroids as adjunctive therapy in patients with severe community-acquired... (Review)
Review
PURPOSE OF REVIEW
This review aims to evaluate the evidence and recommendations for the prescription of corticosteroids as adjunctive therapy in patients with severe community-acquired pneumonia.
RECENT FINDINGS
Corticosteroids have been prescribed with the objective to attenuate the marked and persistent activation of the immune system. However, some causes of community-acquired pneumonia, namely viral, are associated with unexpected low levels of cytokines and depressed cellular immunity. As a result, several recent randomized controlled trials and large prospective observational studies repeatedly showed that corticosteroids had no impact on survival, and in some types of pneumonia like influenza, its use was associated with potential harmful effects like invasive aspergillosis. Apart from this, adverse effects, namely hyperglycemia, superinfections and increased length-of-stay, were frequent findings in the corticosteroid-treated patients.
SUMMARY
According to the current evidence, corticosteroids are recommended in Pneumocystis jiroveci pneumonia in HIV-infected patients and recommendations are against its use in influenza. In all other forms of severe community-acquired pneumonia, with the exclusion of SARS-CoV-2 pneumonia, the strength of the evidence does not support the safe and widespread use of corticosteroids as adjunctive therapy. Further studies are needed to identify subgroups of severe community-acquired pneumonia that can benefit or not from corticosteroids.
Topics: Adrenal Cortex Hormones; Clinical Decision-Making; Combined Modality Therapy; Community-Acquired Infections; Humans; Pneumonia; Practice Guidelines as Topic; Safety
PubMed: 33394726
DOI: 10.1097/QCO.0000000000000709 -
Critical Reviews in Oncology/hematology Apr 2023Antibody-drug conjugates (ADCs) have demonstrated significant efficacy in treating solid tumors. However, the occurrence of ADC drug-associated pneumonitis can limit the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antibody-drug conjugates (ADCs) have demonstrated significant efficacy in treating solid tumors. However, the occurrence of ADC drug-associated pneumonitis can limit the use of ADCs or have severe consequences, and we know comparatively little about this.
METHODS
PubMed, EMBASE, and the Cochrane library were exhaustively searched for articles and conference abstracts published before September 30, 2022. Two authors independently extracted data from the included studies. A random-effects model was used to conduct a meta-analysis of the relevant outcomes. Forest plots reflected the incidence rates from each study, and binomial methods were used to calculate the 95 % confidence interval.
RESULTS
This meta-analysis included 7732 patients from 39 studies and evaluated the incidence of ADCs drug-associated pneumonitis which have received market approval for the treatment of solid tumors. The total incidence of solid tumors for all-grade pneumonitis was 5.86 % (95 % CI, 3.54-8.66 %) and for grade ≥3 was 0.68 % (95 % CI, 0.18-1.38 %). The incidence of all-grade pneumonitis was 5.08 % (95 % CI, 2.76-7.96 %) and for grade ≥3 was 0.57 % (95 % CI, 0.10-1.29 %) with ADC monotherapy. The incidence of all-grade and grade ≥3 pneumonitis in trastuzumab deruxtecan (T-DXd) was 13.58 % (95 % CI, 9.43-18.29 %) and 2.19 % (95 % CI, 0.94-3.81 %), respectively, the highest in ADC therapy. Total incidence of all-grade pneumonitis was 10.58 % (95 % CI, 4.34-18.81 %) and for grade ≥3 pneumonitis was 1.29 % (95 % CI, 0.22-2.92 %) with ADC combination therapy. The incidence of pneumonitis was higher with combination therapy than with monotherapy in both all-grade and grade ≥3 groups, but there was no statistical significance (P = .138 and P = .281, respectively). The incidence of ADC-associated pneumonitis in non-small cell lung cancer (NSCLC) was 22.18 % (95 % CI, 2.14-52.61 %), the highest among solid tumors. The 11 included studies reported 21 pneumonitis-related deaths.
CONCLUSIONS
Our findings will assist clinicians in choosing the optimal therapeutic options for patients with solid tumors treated with ADCs.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Incidence; Lung Neoplasms; Pneumonia; Immunoconjugates
PubMed: 36907365
DOI: 10.1016/j.critrevonc.2023.103960 -
Frontiers in Immunology 2023Pneumonitis is one of the most common adverse events induced by the use of immune checkpoint inhibitors (ICI), accounting for a 20% of all ICI-associated deaths. Despite... (Review)
Review
BACKGROUND
Pneumonitis is one of the most common adverse events induced by the use of immune checkpoint inhibitors (ICI), accounting for a 20% of all ICI-associated deaths. Despite numerous efforts to identify risk factors and develop predictive models, there is no clinically deployed risk prediction model for patient risk stratification or for guiding subsequent monitoring. We believe this is due to systemic suboptimal approaches in study designs and methodologies in the literature. The nature and prevalence of different methodological approaches has not been thoroughly examined in prior systematic reviews.
METHODS
The PubMed, medRxiv and bioRxiv databases were used to identify studies that aimed at risk factor discovery and/or risk prediction model development for ICI-induced pneumonitis (ICI pneumonitis). Studies were then analysed to identify common methodological pitfalls and their contribution to the risk of bias, assessed using the QUIPS and PROBAST tools.
RESULTS
There were 51 manuscripts eligible for the review, with Japan-based studies over-represented, being nearly half (24/51) of all papers considered. Only 2/51 studies had a low risk of bias overall. Common bias-inducing practices included unclear diagnostic method or potential misdiagnosis, lack of multiple testing correction, the use of univariate analysis for selecting features for multivariable analysis, discretization of continuous variables, and inappropriate handling of missing values. Results from the risk model development studies were also likely to have been overoptimistic due to lack of holdout sets.
CONCLUSIONS
Studies with low risk of bias in their methodology are lacking in the existing literature. High-quality risk factor identification and risk model development studies are urgently required by the community to give the best chance of them progressing into a clinically deployable risk prediction model. Recommendations and alternative approaches for reducing the risk of bias were also discussed to guide future studies.
Topics: Humans; Japan; Pneumonia; Risk Factors; Systematic Reviews as Topic
PubMed: 37818359
DOI: 10.3389/fimmu.2023.1228812 -
International Journal of Molecular... Aug 2019Human cytomegalovirus (HCMV) is an opportunistic pathogen causing disease mainly in immunocompromised patients or after congenital infection. HCMV infection of the... (Review)
Review
Human cytomegalovirus (HCMV) is an opportunistic pathogen causing disease mainly in immunocompromised patients or after congenital infection. HCMV infection of the respiratory tract leads to pneumonitis in the immunocompromised host, which is often associated with a bad clinical course. The related mouse cytomegalovirus (MCMV) likewise exhibits a distinct tropism for the lung and thus provides an elegant model to study host-pathogen interaction. Accordingly, fundamental features of cytomegalovirus (CMV) pneumonitis have been discovered in mice that correlate with clinical data obtained from humans. Recent studies have provided insight into MCMV cell tropism and localized inflammation after infection of the respiratory tract. Accordingly, the nodular inflammatory focus (NIF) has been identified as the anatomical correlate of immune control in lungs. Several hematopoietic cells involved in antiviral immunity reside in NIFs and their key effector molecules have been deciphered. Here, we review what has been learned from the mouse model with focus on the microanatomy of infection sites and antiviral immunity in MCMV pneumonitis.
Topics: Animals; Cytomegalovirus; Cytomegalovirus Infections; Disease Models, Animal; Disease Susceptibility; Host-Pathogen Interactions; Humans; Immunity; Pneumonia, Viral; Viral Tropism
PubMed: 31398860
DOI: 10.3390/ijms20163865 -
Immunological Reviews Sep 2023Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. However, their use is frequently associated with immune-related adverse events (irAEs)... (Review)
Review
Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. However, their use is frequently associated with immune-related adverse events (irAEs) potentially affecting any organ. The mechanisms mediating such irAEs remain poorly understood and biomarkers to predict the development of irAEs are lacking. Growing evidence shows the importance of self-antigens in mediating irAEs during ICI therapy, in particular the well-described melanocyte differentiation antigens in melanoma patients. This review will focus on two novel classes of self-antigens involved in mediating autoimmune skin toxicity and pneumonitis in non-small cell lung cancer patients treated with immunotherapy. T cells specific for these self-antigens are thought to not only mediate irAEs but are thought to simultaneously mediate anti-tumor responses and are therefore associated with both autoimmune toxicity and response to ICI therapy. We further discuss emerging cellular and proteomic immune signatures of irAEs that may serve as biomarkers to help predict which patients are at higher risk of developing these irAEs. The determination of new tumor antigens involved in ICI therapy and the identification of related biomarkers brings us a step forward in the mechanistic understanding of ICIs and will help to monitor patients at higher risk of developing irAEs. Lastly, we discuss the current challenges in collecting research samples for the study of ICI-related mechanisms and in distinguishing between immune signatures of response and those of irAEs.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Autoimmunity; Proteomics; Lung Neoplasms; Neoplasms; Skin Diseases; Autoantigens; Pneumonia
PubMed: 37548043
DOI: 10.1111/imr.13258