scholarly journals High‐dose corticosteroid use and risk of hospitalization for infection in patients treated with immune checkpoint inhibitors––A nationwide register‐based cohort study

2021 ◽  
Author(s):  
Signe Sørup ◽  
Bianka Darvalics ◽  
Leo Russo ◽  
Dina Oksen ◽  
Francois‐Xavier Lamy ◽  
...  
Keyword(s):  
Cohort Study ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
High Dose ◽  
High Dose Corticosteroid ◽  
Dose Corticosteroid

Effect of high-dose corticosteroid use on efficacy of immune checkpoint inhibitors in patients with renal cell carcinoma (RCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4583-4583
Author(s):  
Chris Labaki ◽  
Sarah Abou Alaiwi ◽  
Andrew Lachlan Schmidt ◽  
Talal El Zarif ◽  
Ziad Bakouny ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Univariate Analysis ◽  
High Dose ◽  
Line Of Therapy

4583 Background: The use of High-Dose Corticosteroids (HDC) has been linked to poor outcomes in patients with lung cancer treated with immune checkpoint inhibitors (ICIs) (Ricciuti B, JCO, 2019). There is no data on the effect of HDC on renal cell carcinoma patients (RCC) treated with immunotherapy. We hypothesized that HDC use would be associated with worse outcomes in RCC patients receiving ICIs. Methods: This study evaluated a retrospective cohort of patients with RCC at Dana-Farber Cancer Institute in Boston, MA. Clinical information including demographics, IMDC risk score, RCC histology, steroid administration, ICI regimen, line of therapy, time to treatment failure (TTF) and overall survival (OS) were collected. Patients were divided into those receiving HDC (prednisone ≥10 mg or equivalent for ≥ 1 week, HDC group) or not receiving HDC (No-HDC group). HDC administration was evaluated in relation to TTF and OS in a univariate analysis (Log-rank test) and a multivariate analysis (Cox regression). Results: 190 patients with RCC receiving ICIs were included, with a median age of 59 years. HDC were administered to 56 patients and 134 patients received no (N= 116) or only low-dose (N=18) steroids. In the HDC group, 40 patients received steroids for immune-related adverse events, 8 for other cancer-related indications, and 8 for non-oncological indications. There was no difference in TTF between the HDC and No-HDC groups (12-mo TTF rate: 34.8 vs. 32.3%, respectively; log-rank p=0.65). Similarly, there was no difference in OS between the HDC and No-HDC groups (36-mo OS rate: 56.7 vs. 62.4%, respectively; log-rank p=0.97). After adjusting for IMDC risk group, RCC histology, ICI regimen type, and line of therapy, TTF and OS did not differ in the HDC group as compared to No-HDC group (HR=1.14 [95%CI: 0.80-1.62], p=0.44 and HR=1.17 [95%CI: 0.65-2.11], p=0.59, respectively). Conclusions: In this retrospective study of patients with RCC treated with ICIs, administration of high-dose corticosteroids was not associated with worse outcomes.[Table: see text]

scholarly journals Challenge of immune-mediated adverse reactions in the emergency department

2019 ◽  
Vol 36 (6) ◽  
pp. 369-377 ◽  
Author(s):  
Gregory A Daniels ◽  
Angela D Guerrera ◽  
Donna Katz ◽  
Jayne Viets-Upchurch
Keyword(s):  
Immune System ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Adverse Reactions ◽  
Checkpoint Inhibitors ◽  
Immune Checkpoints ◽  
High Dose ◽  
Clear Understanding ◽  
Immune Mediated ◽  
Multiple Drugs

Multiple drugs of a new class of cancer treatments called immune checkpoint inhibitors, which work by enabling the immune system to attack tumour cells, have been approved for a variety of indications in recent years. Immune checkpoints, such as cytotoxic T-lymphocyte antigen-4 and programmed death-1, are part of the normal immune system and regulate immune activation. Treatment with inhibitors of these checkpoints can significantly improve response rates, progression-free survival and overall survival of patients with cancer; it can also result in adverse reactions that present similarly to other conditions. These immune-mediated adverse reactions (IMARs) are most commonly gastrointestinal, respiratory, endocrine or dermatologic. Although patients’ presentations may appear similar to other types of cancer therapy, the underlying causes, and consequently their management, may differ. Prompt recognition is critical because, with appropriate management, most IMARs resolve and patients can continue receiving immune checkpoint inhibitor treatment. Rarely, these IMARs may be life-threatening and escape detection from the usual evaluations in the emergency environment. Given the unusual spectrum and mechanism of IMARs arising from immune checkpoint inhibitors, emergency departmentED staff require a clear understanding of the evaluation of IMARs to enable them to appropriately assess and treat these patients. Treatment of IMARs, most often with high-dose steroids, differs from chemotherapy-related adverse events and when possible should be coordinated with the treating oncologist. This review summarises the ED presentation and management of IMARs arising from immune checkpoint inhibitors and includes recommendations for tools and resources for ED healthcare professionals.

scholarly journals The mechanisms of acute interstitial nephritis in the era of immune checkpoint inhibitors in melanoma

2019 ◽  
Vol 11 ◽  
pp. 175883591987554 ◽  
Author(s):  
Marco Tucci ◽  
Anna Passarelli ◽  
Annalisa Todisco ◽  
Francesco Mannavola ◽  
Luigia Stefania Stucci ◽  
...  
Keyword(s):  
Renal Function ◽  
Interstitial Nephritis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Acute Interstitial Nephritis ◽  
Clinical State ◽  
High Dose ◽  
Systemic Symptoms ◽  
The Impact

Treatment with immune checkpoint inhibitors (ICIs) has improved the prognosis of patients with a number of types of cancer, but the frequent development of immune-related adverse effects (irAEs) can worsen the outcome. The most common irAEs involve the gastrointestinal, cutaneous, and endocrine systems, but nephrotoxicity, resulting from damage to the tubule-interstitial compartment, may occur in some patients. The early phases of acute interstitial nephritis (AIN) are characterized by systemic symptoms that indicate a poor clinical state as well as a mild deterioration of renal function. Tubular injury is due to a direct effect mediated by cytotoxic CD8+ T cells, which sustain the local production of pro-inflammatory cytokines that progressively impair renal function. The treatment of AIN is mainly based on high-dose steroids, which in most instances leads to the recovery of renal function. However, the premature discontinuation of ICI therapy may prevent the impact of treatment on the clinical progression of the malignancy. Adequately addressing irAEs requires a standardized therapy that is based on the results of large clinical trials.

scholarly journals Case Report: A Case of Trimethoprim/Sulfamethoxazole-Triggered Hypotensive Shock: Cytokine Release Syndrome Related to Immune Checkpoint Inhibitors and Drug-Induced Hypersensitivity Syndrome

2021 ◽  
Vol 11 ◽  
Author(s):  
Tetsuya Urasaki ◽  
Makiko Ono ◽  
Toshiaki Mochizuki ◽  
Koichi Takeda ◽  
Aya Nishizawa ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Interstitial Pneumonitis ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Hypersensitivity Syndrome ◽  
High Dose ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Drug Induced ◽  
Prophylactic Administration

Currently, only a few reports exist on the cytokine release syndrome (CRS) as one of the severe immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs). Notably, it is very rare that grade 4 CRS related to ICI therapy overlaps with the drug-induced hypersensitivity syndrome (DiHS). A 46-year old woman with metastatic kidney cancer had grade 3 interstitial pneumonitis induced by four cycles of combination therapy of anti-programmed death-1 and anti-cytotoxic T lymphocyte-4 antibodies after right cytoreductive nephrectomy. Prophylactic administration of trimethoprim/sulfamethoxazole (TMP/SMX) was started concomitantly with prednisolone therapy to treat the interstitial pneumonitis. She developed hypotensive shock when reducing the dosage of prednisolone, and required intubation and ventilation using vasopressors at the intensive care unit. She subsequently exhibited prominent leukocytosis and an increased level of C-reactive protein, suggesting markedly increased cytokine levels. Interestingly, facial edema and erythema increased in association with pyrexia, leukocytosis, liver dysfunction, and renal failure, suggesting that she developed DiHS. She received hemodialysis three times, a plasma exchange, and anti-interleukin-6 therapy to treat severe renal dysfunction, a thrombotic thrombocytopenic purpura-suspected condition, and possible grade 4 CRS, respectively. Although these therapies did not elicit sufficient effects, high-dose administration of intravenous immunoglobulin was successful. With steroid mini-pulse therapy and the subsequent administration of prednisolone, she recovered successfully. To the best of our knowledge, this is the first report that ICIs and TMP/SMX can induce hypotensive shock accompanied with CRS and DiHS during immunosuppressive therapy for an irAE. Importantly, the prophylactic administration of TMP/SMX should be performed cautiously to avoid severe drug reactions such as CRS or DiHS.

scholarly journals Fulminant Hepatic Failure after Chemosaturation with Percutaneous Hepatic Perfusion and Nivolumab in a Patient with Metastatic Uveal Melanoma

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Lindsey Teal ◽  
Jeffrey Yorio
Keyword(s):  
Liver Metastases ◽  
Uveal Melanoma ◽  
Fulminant Hepatic Failure ◽  
Immune Checkpoint ◽  
Hepatic Failure ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
High Dose ◽  
Hepatic Perfusion ◽  
Percutaneous Hepatic Perfusion

Immune checkpoint inhibitors, such as nivolumab, a programmed death receptor-1 (PD-1) inhibitor, have dramatically improved the treatment of advanced melanomas. Chemosaturation with percutaneous hepatic perfusion (PHP) delivers chemotherapy in high doses directly to the liver and is a potentially effective treatment modality in metastatic uveal melanoma with liver metastases. Its safety and effectiveness have not been studied in patients also receiving immunotherapy. A 46-year-old male with a history of uveal melanoma of the right eye was found to have liver metastases. He was treated with PHP using high-dose melphalan for 6 months with a partial response followed by progression. Two months after his last PHP treatment, the patient was started on nivolumab. After two doses of nivolumab, the patient developed severe hepatitis that progressed to fulminant hepatic failure and death despite treatment with high-dose corticosteroids and mycophenolate mofetil. Nivolumab and other immune checkpoint inhibitors have been effective in treating advanced melanoma and extending life. However, there are serious immune adverse events that can occur. While hepatitis after taking nivolumab has been documented, fulminant hepatic failure is rare. We believe that prior PHP treatment contributed to the severity of the hepatitis and, ultimately, fulminant hepatic failure. To our knowledge, this is the only case of fulminant hepatic failure secondary to a checkpoint inhibitor with preceding PHP. Specific precautions should be made in patients who have been exposed to PHP in the past, and further studies should be done to assess the safety of using checkpoint inhibitors after PHP.

scholarly journals Pattern and impact of hepatic adverse events encountered during immune checkpoint inhibitors – A territory‐wide cohort study

2020 ◽  
Vol 9 (19) ◽  
pp. 7052-7061 ◽  
Author(s):  
Stephen Lam Chan ◽  
Terry Cheuk‐Fung Yip ◽  
Vincent Wai‐Sun Wong ◽  
Yee‐Kit Tse ◽  
Becky Wing‐Yan Yuen ◽  
...  
Keyword(s):  
Cohort Study ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors

scholarly journals Risk of asthma in children diagnosed with bronchiolitis during infancy: protocol of a longitudinal cohort study linking emergency department-based clinical data to provincial health administrative databases

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e048823
Author(s):  
Kawsari Abdullah ◽  
Deshayne B Fell ◽  
Dhenuka Radhakrishnan ◽  
Steven Hawken ◽  
David W Johnson ◽  
...  
Keyword(s):  
Cohort Study ◽  
Prediction Models ◽  
Combined Therapy ◽  
Longitudinal Cohort Study ◽  
Administrative Databases ◽  
High Dose ◽  
High Dose Corticosteroid ◽  
Longitudinal Cohort ◽  
Asthma In Children ◽  
Dose Corticosteroid

IntroductionThe Canadian Bronchiolitis Epinephrine Steroid Trial (CanBEST) and the Bronchiolitis Severity Cohort (BSC) study enrolled infants with bronchiolitis during the first year of life. The CanBEST trial suggested that treatment of infants with a combined therapy of high-dose corticosteroids and nebulised epinephrine reduced the risk of admission to hospital. Our study aims to—(1) quantify the risk of developing asthma by age 5 and 10 years in children treated with high-dose corticosteroid and epinephrine for bronchiolitis during infancy, (2) identify risk factors associated with development of asthma in children with bronchiolitis during infancy, (3) develop asthma prediction models for children diagnosed with bronchiolitis during infancy.Methods and analysisWe propose a longitudinal cohort study in which we will link data from the CanBEST and BSC study with routinely collected data from provincial health administrative databases. Our outcome is asthma incidence measured using a validated health administrative data algorithm. Primary exposure will be treatment with a combined therapy of high-dose corticosteroids and nebulised epinephrine for bronchiolitis. Covariates will include type of viral pathogen, disease severity, medication use, maternal, prenatal, postnatal and demographic factors and variables related to health service utilisation for acute lower respiratory tract infection. The risk associated with development of asthma in children treated with high-dose corticosteroid and epinephrine for bronchiolitis will be assessed using multivariable Cox proportional hazards regression models. Prediction models will be developed using multivariable logistic regression analysis and internally validated using a bootstrap approach.Ethics and disseminationOur study has been approved by the ethics board of all four participating sites of the CanBEST and BSC study. Finding of the study will be disseminated to the academic community and relevant stakeholders through conferences and peer-reviewed publications.Trial registration numberISRCTN56745572; Post-results.

Thrombotic events in patients treated with immune checkpoint inhibitors for non-small cell lung cancer: A retrospective multicentric cohort study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21198-e21198
Author(s):  
Xavier Deschenes-Simard ◽  
Loik Galland ◽  
Florence Blais ◽  
Antoine Desilets ◽  
Julie Malo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cohort Study ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

e21198 Background: Venous thromboembolism is a frequent complication of non-small cell lung cancer (NSCLC) and is associated with a worse prognosis, a reduced quality of life, and increased healthcare costs. Immune checkpoint inhibitors (ICI) are revolutionizing the management of NSCLC, but little is known about their impact on thrombosis. This study aims to define the incidence and clinical relevance of thrombosis in NSCLC patients receiving these treatments. Methods: A retrospective multicentric cohort study including 593 patients from three centers in Canada and France was performed. The cumulative incidence of venous thrombotic events after ICIs was calculated, and the impact of these events on survival and response to treatment was determined. Finally, univariate log-rank tests were performed to identify thrombosis risk factors. Results: The incidence of venous thrombosis in the cohort was 9.9% for an incidence rate of 76.5 thrombosis per 1000 person-years, with most thromboses occurring rapidly after treatment initiation. Thrombosis was not correlated with overall survival, progression-free survival, or objective response to ICIs (summarized in the table below). Age ˂ 65 years old (HR = 1.66; 95 % CI = 1.00 – 2.82) and a delay of less than 12 months from diagnosis to the first ICI treatment (HR = 1.74; 95 % CI = 1.03 – 2.87) were associated with an increased risk of thrombosis. Tumors with PD-L1 > 1% were associated with more thrombosis in the first year since the beginning of therapy (HR = 3.06; 95 % CI = 1.19 – 4.76, p=0.015). Conclusions: This study suggests that the time distribution and incidence of thrombotic events in NSCLC patients treated with ICI are comparable to what is reported in other cohorts of patients treated with chemotherapy. In our cohort, thrombosis was not a prognostic factor for survival or response to therapy. Patient age < 65 and tumors with PD-L1 > 1% were associated to a higher risk of thrombotic events.[Table: see text]

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