scholarly journals Releasing the brakes: a case report of pulmonary arterial hypertension induced by immune checkpoint inhibitor therapy

2020 ◽  
Vol 10 (4) ◽  
pp. 204589402096096 ◽  
Author(s):  
Matthew Glick ◽  
Chase Baxter ◽  
David Lopez ◽  
Kashif Mufti ◽  
Stephen Sawada ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Lupus Erythematosus ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Checkpoint Inhibitor Therapy ◽  
Pulmonary Arterial

Immune checkpoint inhibitors successfully treat various malignancies by inducing an immune response to tumor cells. However, their use has been associated with a variety of autoimmune disorders, such as diabetes, hepatitis, and pneumonitis. Pulmonary arterial hypertension due to checkpoint inhibitor use has not yet been described. We present a novel case of pulmonary arterial hypertension associated with systemic lupus erythematosus and Sjogren’s syndrome overlap that was induced by therapy with the checkpoint inhibitor durvalumab.

Evaluation of arthralgias in adult oncology patients receiving immune checkpoint inhibitors

2019 ◽  
Vol 25 (8) ◽  
pp. 1867-1872 ◽  
Author(s):  
Jenessa Lee ◽  
Anastasia Graham ◽  
Amy Sion
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Retrospective Chart Review ◽  
Inhibitor Therapy ◽  
Time To Event ◽  
History Of ◽  
Checkpoint Inhibitor Therapy

Immune checkpoint inhibitors are being commonly used as anticancer therapies to treat malignancies. Immune checkpoint inhibitors have been associated with numerous immune-related adverse events (irAEs). IrAEs are well documented; however, rheumatic irAEs are infrequently reported in published literature. The objective of this single-center retrospective chart review study was to evaluate the incidence of arthralgias with immune checkpoint inhibitor therapy as well as the management of these immune-related events. Patients were included if they received one or more doses of nivolumab, pembrolizumab, atezolizumab, ipilimumab, or a combination of agents within the last year. Exclusion criteria included documented history of autoimmune disease, off-label use of immune checkpoint inhibitor, and non-FDA-approved weight-based dosing. This study included 98 patients for review and identified 11 patients that developed arthralgias with immune checkpoint inhibitor therapy. Median time to event was 63 days. Seven patients were treated with corticosteroids. Immune checkpoint inhibitor therapy was held in six patients with arthralgias. Inflammatory markers were collected for six patients and elevated in four of these cases. One patient was referred to rheumatology. The three patients who had grading of arthralgias were not managed optimally according to guideline recommendations. These findings show that 11% of patients treated with immune checkpoint inhibitors had documented arthralgias, consistent with previous reports in the literature. Also, the report shows that management and treatment of these events at our institution was not consistent between providers. Lastly, collaboration with rheumatology may be essential in managing arthralgias and other rheumatologic irAEs.

scholarly journals Incidence, risk factors and outcomes of venous and arterial thromboembolism in immune checkpoint inhibitor therapy

Blood ◽  
2020 ◽  
Author(s):  
Florian Moik ◽  
Wei-Shin Evelyn Chan ◽  
Sarah Wiedemann ◽  
Christoph Hoeller ◽  
Felix Tuchmann ◽  
...  
Keyword(s):  
Risk Factors ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Hazard Ratio ◽  
Arterial Thromboembolism ◽  
Patients With Cancer ◽  
Checkpoint Inhibitor Therapy

The risk of venous and arterial thromboembolism (VTE/ATE) associated with immune checkpoint inhibitors is currently unclear, and clinical trials evaluating these agents in patients with cancer did not provide information. Our aim was to quantify risk of VTE/ATE in a cohort of patients treated with immune checkpoint inhibitors, explore clinical impact, and investigate potential clinical risk factors. Patients treated with an immune checkpoint inhibitor at the Medical University of Vienna from 2015-2018 were identified using the in-house pharmacy records (n=672; most frequent entities: 30.4% melanoma, 24.1% non-small-cell lung cancer; 86% stage-IV-disease). A retrospective chart-review was performed to screen for VTE and/or ATE. Cumulative incidences and between-group differences were analysed within a competing-risk framework. Multi-state modelling was applied to study the impact of VTE/ATE on mortality. Over a median follow-up of 8.5 months, 47 VTE and 9 ATE were observed. Cumulative incidences of VTE and ATE were 12.9% [95% confidence interval (CI): 8.2-18.5)] and 1.8% [95%CI: 0.7-3.6]. Occurrence of VTE was associated with increased mortality (transition hazard-ratio (THR): 3.09 [95%CI: 2.07-4.60]. History of VTE predicted VTE occurrence (subdistribution hazard ratio (SHR): 3.69 [2.00-6.81]) and distant metastasis was non-significantly associated with VTE risk (SHR: 1.71 [95%CI: 0.62-4.73]). No association of VTE with ECOG performance-status, Charlson-Comorbidity-Index or the Khorana-score was observed, and rates of VTE were comparable among subgroups of tumour types and checkpoint-inhibitory agents. In conclusion, patients with cancer under immune checkpoint inhibitor therapy are at high risk of thromboembolism, especially VTE. Furthermore, VTE occurrence was associated with increased risk of mortality.

scholarly journals Neurotoxicities associated with immune checkpoint inhibitor therapy

2020 ◽  
Vol 19 ◽  
Author(s):  
Zhiyi Zhao ◽  
Chunlin Zhang ◽  
Lian Zhou ◽  
Pan Dong ◽  
Lei Shi
Keyword(s):  
Nervous System ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Peripheral Neuropathies ◽  
The Central Nervous System ◽  
Checkpoint Inhibitor Therapy ◽  
Promising Treatment

: Immune checkpoint inhibitors (ICIs) have recently been used as a promising treatment for cancer while their toxicity and immune-related side effects can involve in any organ, including the nervous system. In contrast to other immune-related adverse events (irAEs), neurological irAEs (nAEs) are rare, with varying incidence and symptoms complexity. Although nAEs are uncommon, they can sometimes be severe and even lead to death. However, little attention has been paid to nAEs and the literatures are mostly clinical reports with only a few cases. We therefore conducted the present review with the aim of providing a comprehensive introduction of nAEs. In this review, we summarized various nAEs, including meningitis, encephalitis and hypophysitis in the central nervous system, and myositis, myasthenia gravis and peripheral neuropathies in the peripheral system. We also reviewed the current diagnosis and treatment methods for nAEs commonly used in clinical practice. In addition, we discussed about potential mechanisms regarding nAEs and proposed the possible approaches to preventing the risk of nAEs in patients treated with ICIs. There's still a lot to learn, such as whether and why patients with nAEs respond better to ICI-therapy. The mechanisms and significance of nAEs need to be fully clarified to address these issues and to optimize the treatment strategy.

New onset diabetes with ketoacidosis following nivolumab immunotherapy: A case report and review of literature

2020 ◽  
pp. 107815522094394
Author(s):  
Lukas Delasos ◽  
Christopher Bazewicz ◽  
Aleksandra Sliwinska ◽  
Nerea Lopetegui Lia ◽  
James Vredenburgh
Keyword(s):  
Diabetes Mellitus ◽  
Case Report ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Programmed Death ◽  
Checkpoint Inhibitor Therapy

Introduction Immune-checkpoint inhibitors have become an increasingly popular form of systemic therapy for cancer treatment. Their use has proven to be so effective that certain regimens have gained approval as first-line therapy for various solid tumor types. The most common and well-studied forms of immunotherapy include agents that target cytotoxic T-lymphocyte antigen-4, programmed death-1, and programmed death ligand-1. These therapies act by blocking signaling between immune cells and cancer cells which subsequently augment T cell-mediated destruction of tumor cells. Case report Here, we report a case of a 77-year-old black male with no history of or risk factors for diabetes mellitus who presented with acute onset of diabetic ketoacidosis after beginning immunotherapy with nivolumab for metastatic high-grade neuroendocrine tumor of the lung. He was admitted and treated for diabetic ketoacidosis but required prolonged use of an insulin infusion with frequent need of intravenous dextrose due to labile blood sugars. The patient was eventually discharged and discontinued further immunotherapy with nivolumab. Discussion Due to the unique mechanisms by which immune-checkpoint inhibitors cause immune-mediated destruction of tumor cells, clinicians may be challenged with their associated autoimmune complications referred to as immune-related adverse events. In particular, the incidence of endocrine dysfunction following immune-checkpoint inhibitor therapy is approximately 12%, with the development of insulin-dependent diabetes mellitus being a rare complication. Increasing awareness of immune-related adverse events is essential for the early recognition and effective management of patients who present with life-threatening complications related to immune-checkpoint inhibitor therapy.

scholarly journals Adverse effects of immune checkpoint inhibitor therapies on right ventricular function and pulmonary arterial dilatation

2021 ◽  
Vol 11 (1) ◽  
pp. 204589402199223
Author(s):  
Ruben Mylvaganam ◽  
Ryan Avery ◽  
Isaac Goldberg ◽  
Courtney Makowski ◽  
Ravi Kalhan ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Inhibitor Therapy ◽  
Percent Change ◽  
Checkpoint Inhibitor Therapy

Immunologic risk factors contribute to endothelial dysfunction and development of pulmonary vascular disease. Immune checkpoint inhibitors, used as immunotherapies for malignancies, have a wide range of reported immune-related adverse events. We retrospectively describe the impact of immune checkpoint inhibitors on the development of pulmonary vascular injury and right ventricular dysfunction as compared across both computed tomography and transthoracic echocardiography. Twenty-four of 389 patients treated with immune checkpoint inhibitors at a single academic center between 2015 and 2019 were evaluated. Thirteen (54%) patients were treated with anti-programmed cell death receptor 1 (PD-1), 8 (33%) with anti-programmed death receptor ligand 1 (PD-L1) therapy, and 3 (13%) with combination anti-PD-1 and anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) therapy. At a median of 85 days of immune checkpoint inhibitor therapy, RVfwLS significantly increased from –20.6% to –16.7% ( p = 0.002). After a median of 59 days of immune checkpoint inhibitor therapy, median pulmonary artery to aorta ratio worsened from 0.83 to 0.89 ( p = 0.03). There was an correlation of duration of immune checkpoint inhibitor therapy (β = –0.574, p = 0.003) with percent change in RVfwLS. Patients who received anti-PD-1 therapy (β = –0.796, p = 0.001) showed the greatest correlation of duration of immune checkpoint inhibitor therapy with percent change in RVfwLS. Exposure to immune checkpoint inhibitors are associated with RV dysfunction and vascular changes as measured by strain and computed tomography, respectively.

scholarly journals Enterococcus peptidoglycan remodeling promotes immune checkpoint inhibitor therapy

2020 ◽  
Author(s):  
Matthew E. Griffin ◽  
Juliel Espinosa ◽  
Jessica L. Becker ◽  
Jyoti K. Jha ◽  
Gary R. Fanger ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Immune Checkpoint ◽  
Molecular Mechanisms ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Mouse Tumor ◽  
Peptidoglycan Hydrolases ◽  
Checkpoint Inhibitor Therapy ◽  
Specific Species

AbstractThe antitumor efficacy of cancer immunotherapy has been correlated with specific species within the gut microbiota. However, molecular mechanisms by which these microbes affect host response to immunotherapy remain elusive. Here we show that specific members of the bacterial genus Enterococcus can promote anti-PD-L1 immunotherapy in mouse tumor models. The active enterococci express and secrete orthologs of the NlpC/p60 peptidoglycan hydrolase SagA that generate immune-active muropeptides. Expression of SagA in non-protective E. faecalis was sufficient to promote antitumor activity of clinically approved checkpoint targets, and its activity required the peptidoglycan sensor Nod2. Notably, SagA-engineered probiotics or synthetic muropeptides also promoted checkpoint inhibitor antitumor activity. Our data suggest that microbiota species with unique peptidoglycan remodeling activity may enhance immunotherapy and could be leveraged for next-generation adjuvants.One Sentence SummaryA conserved family of secreted NlpC/p60 peptidoglycan hydrolases from Enterococcus promote antitumor activity of immune checkpoint inhibitors.

Efficacy of immunotherapy in hepatocholangiocarcinoma (HCC-CC): Proof of concept.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16194-e16194
Author(s):  
Osama Diab ◽  
Maloree Khan ◽  
Saqib Abbasi ◽  
Anwaar Saeed ◽  
Anup Kasi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Line Treatment ◽  
First Line ◽  
Liver Cancers ◽  
First Line Treatment

e16194 Background: Hepatocholangiocarcinoma (HCC-CC) is a rare form of cancer with a poor prognosis. Of all primary liver cancers, the incidence of HCC-CC ranges from 0.4 to 14.2%. HCC-CC is a mixed carcinoma with findings of both hepatocellular carcinoma and cholangiocarcinoma. Immune checkpoint inhibitors are a potent first line treatment in hepatocellular carcinoma with multiple clinical trial showing effectiveness in cholangiocarcinoma. HCC-CC has limited proven treatment options as patients are generally excluded from clinical trials. In this study we reviewed outcomes of patients with HCC-CC who received immune checkpoint inhibitor in a single center. Methods: Records of patients who had a pathological confirmed HCC-CC by a subspecialized hepatic pathologist at the University of Kansas medical center were reviewed. We identified 6 patients with locally advanced unresectable or metastatic HCC-CC that received immune checkpoint inhibitor between February 2017 and January 2021. Baseline characteristics were obtained, as well as best response, line of therapy, and duration of response. Results: Of the six patients 4 (66%) received PD-1 inhibitor alone and 2 (34%) received combination therapy with CTLA-4 inhibitor for the treatment of HCC-CC. There were 3 (50%) females and 6 (100%) with prior hepatitis C infection. four (66%) patients had metastatic disease and 2 had locally unresectable advanced disease. Objective response rate was 83.3%. One patient achieved complete response and had a treatment holiday after receiving treatment for 2 years, and restarted immunotherapy upon relapse. Four patients had a partial response, of which two passed away after disease progression. One patient had stable disease on 2 different lines of immunotherapy then progressed. Of those who responded, one patient received immunotherapy, 3 (50%) received liver directed therapy and two received chemotherapy or Lenvatinib as first line treatment (Table). Conclusions: Immune checkpoint inhibitors demonstrate potential activity in patients with HCC-CC without unexpected side effect in this unmet need high-risk population. Larger studies are needed to confirm activity and efficacy in this setting.[Table: see text]

Peritoneal melanosis associated with metastatic melanoma previously treated with targeted and immune checkpoint inhibitor therapy

2021 ◽  
Vol 14 (1) ◽  
pp. e238235
Author(s):  
Kwang Kiat Sim ◽  
Katie Connell ◽  
Mayank Bhandari ◽  
David Paton
Keyword(s):  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Inhibitor Therapy ◽  
Tumour Regression ◽  
Benign Condition ◽  
Checkpoint Inhibitor Therapy ◽  
Previously Treated

Peritoneal melanosis is an uncommon benign condition, the pathophysiology of which is unclear. Macroscopically, it appears as diffuse dark brown or black pigmentation within the peritoneum, mimicking more sinister conditions such as metastatic melanoma. It has been described in a variety of contexts, but only exceedingly rarely in association with metastatic melanoma, with only two previous published case reports. We present a case of peritoneal melanosis associated with metastatic melanoma involving the spleen, previously treated with targeted and immune checkpoint inhibitor therapy. With increasing reports of melanoma regression manifesting as cutaneous tumorous melanosis in patients treated with immune checkpoint inhibitors, we postulate that, similarly, immunotherapy and tumour regression might have a role to play in the pathogenesis of the peritoneal pigmentation in this case.

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