scholarly journals Cancer patients receiving immune checkpoint inhibitor therapy are at an increased risk for atherosclerotic cardiovascular disease

2020 ◽  
Vol 8 (1) ◽  
pp. e000300 ◽  
Author(s):  
Esther Lutgens ◽  
Tom T.P. Seijkens
Keyword(s):  
Cardiovascular Disease ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Inflammatory Diseases ◽  
Experimental Studies ◽  
Low Grade ◽  
Atherosclerotic Cardiovascular Disease ◽  
Increased Risk ◽  
Immune Checkpoint Proteins

The widespread clinical use of immune checkpoint inhibitors (ICI) has increased our knowledge on their adverse effects on chronic inflammatory diseases. Atherosclerosis, a low-grade lipid-driven inflammatory disease of the larger arteries, is commonly present in cancer patients. A major concern is the adverse effect of ICI on atherosclerosis-related cardiovascular disease, resulting in cardiovascular events, such as myocardial infarction or ischaemic stroke. The effects of ICI on atherosclerosis in cancer patients are incompletely understood, but it is well known that immune checkpoint proteins orchestrate the inflammatory response underlying atherogenesis. This paper addresses the hypothesis that ICI therapy puts cancer patients at an increased risk for atherosclerosis-related cardiovascular disease, that might only become apparent years after ICI therapy. Until clinical and experimental studies have addressed this hypothesis, optimal cardiovascular risk management in ICI-treated patients is opportune to reduce the occurrence of cardiovascular disease in cancer patients and long-term cancer survivors.

Chronic Inflammatory Diseases and Atherosclerotic Cardiovascular Disease: Innocent Bystanders or Partners in Crime?

2018 ◽  
Vol 24 (3) ◽  
pp. 281-290 ◽  
Author(s):  
Peter Riis Hansen
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Inflammatory Diseases ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Chronic Inflammatory Diseases ◽  
Increased Risk ◽  
Shared Risk

Inflammation plays a significant role in atherosclerosis and cardiovascular disease (CVD). Patients with chronic inflammatory diseases are at increased risk of CVD, but it is debated whether this association is causal or dependent on shared risk factors, other exposures, genes, and/or inflammatory pathways. The current review summarizes epidemiological, clinical, and experimental data supporting the role of shared inflammatory mechanisms between atherosclerotic CVD and rheumatoid arthritis, psoriasis, inflammatory bowel disease, and periodontitis, respectively, and provides insights to future prospects in this area of research. Awareness of the role of inflammation in CVD in patients with chronic inflammatory diseases and the potential for anti-inflammatory therapy, e.g., with tumor necrosis factor-α inhibitors, to also reduce atherosclerotic CVD has evolved into guideline- based recommendations. These include regular CVD risk assessment, aggressive treatment of traditional CVD risk factors, and recognition of reduced CVD as an added benefit of strict inflammatory disease control. At present, chronic inflammatory diseases would appear to qualify as partners in crime and not merely innocent bystanders to CVD. However, definite incremental contributions of inflammation versus effects of the complex interplay with other CVD risk factors may never be fully elucidated and for the foreseeable future, inflammation is posed to maintain its current position as both a marker and a maker of CVD, with clinical utility both for identification of patient at risk of CVD and as target for therapy to reduce CVD.

scholarly journals Lights and Shadows on Managing Immune Checkpoint Inhibitors in Oncology during the COVID-19 Era

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1906
Author(s):  
Chiara Burgaletto ◽  
Oronzo Brunetti ◽  
Antonio Munafò ◽  
Renato Bernardini ◽  
Nicola Silvestris ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Viral Infections ◽  
Checkpoint Inhibitors ◽  
Severe Disease ◽  
Inflammatory Phase ◽  
Clinical Observations ◽  
Increased Risk ◽  
The One

Since the start of the global spread of coronavirus disease (COVID-19) pandemic, cancer patients were identified as a specifically susceptible subgroup of the patient population. Several reports have shown that cancer patients have an increased risk of both contracting the infection and of experiencing a more severe disease course, with a rapidly evolving picture associated with higher mortality. The assumption of cancer patients as “COVID-19 vulnerable” has led, irretrievably, to profound changes in the decision making of oncological treatments. Potential justifications for such concerns encompass the cancer-dependent suppression of the immune response, as well as the influence of administration of systemic anticancer treatments, including chemotherapy and immunotherapy. Nevertheless, to date, it is not clear whether the use of immune checkpoint inhibitors (ICIs) in cancer patients is safe, given their modulating effects on the immune system, or that they may rather conceal detrimental consequences. Theoretically, on the one hand, ICIs may enhance the immunological control of viral infections through their immunostimulating mechanisms; on the other hand, they could contribute to the hyper-inflammatory phase of COVID-19, worsening its clinical outcomes. In this study, we report the foremost clinical observations on the safety of ICI administration in cancer patients affected by COVID-19.

scholarly journals Immune checkpoint inhibitor treatment and atherosclerotic cardiovascular disease: an emerging clinical problem

2021 ◽  
Vol 9 (6) ◽  
pp. e002916
Author(s):  
Kikkie Poels ◽  
Suzanne I.M. Neppelenbroek ◽  
Marie José Kersten ◽  
M. Louisa Antoni ◽  
Esther Lutgens ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Immune Checkpoint ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Clinical Problem ◽  
Chronic Inflammatory Disease ◽  
Atherosclerotic Cardiovascular Disease ◽  
Diverse Patient Population ◽  
Artery Disease

Antibody-mediated blockade of co-inhibitory molecules such as cytotoxic T lymphocyte-associated protein 4, PD1 and PDL1 elicits potent antitumor responses and improves the prognosis of many patients with cancer. As these immune checkpoint inhibitors (ICIs) are increasingly prescribed to a diverse patient population, a broad range of adverse effects is emerging. Atherosclerosis, a lipid-driven chronic inflammatory disease of the large arteries, may be aggravated by ICI treatment. In this review, we discuss recent clinical studies that analyze the correlation between ICI use and atherosclerotic cardiovascular disease (CVD). Indeed, several studies report an increased incidence of atherosclerotic CVD after ICI administration, with the occurrence of pathologies such as myocardial infarction, ischemic stroke and coronary artery disease significantly higher after ICI use. Increased awareness and better monitoring of ICI-treated patients can elucidate risk factors that contribute to ICI-induced aggravation of atherosclerosis and identify promising treatment strategies. For now, optimal cardiovascular risk assessment is required to protect ICI-receiving patients and long-term survivors of cancer from the detrimental effects of ICI therapy on atherosclerotic CVD.

scholarly journals Cancer Management during COVID-19 Pandemic: Is Immune Checkpoint Inhibitors-Based Immunotherapy Harmful or Beneficial?

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2237 ◽  
Author(s):  
Silvia Vivarelli ◽  
Luca Falzone ◽  
Caterina Maria Grillo ◽  
Giuseppa Scandurra ◽  
Francesco Torino ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Mechanisms Of Action ◽  
Current Evidence ◽  
Question Mark ◽  
Cancer Management ◽  
Increased Risk ◽  
Anti Cancer

The coronavirus disease 2019 (COVID-19) is currently representing a global health threat especially for fragile individuals, such as cancer patients. It was demonstrated that cancer patients have an increased risk of developing a worse symptomatology upon severe acute respiratory syndrome associated coronavirus-2 (SARS-CoV-2) infection, often leading to hospitalization and intensive care. The consequences of this pandemic for oncology are really heavy, as the entire healthcare system got reorganized. Both oncologists and cancer patients are experiencing rescheduling of treatments and disruptions of appointments with a concurrent surge of fear and stress. In this review all the up-to-date findings, concerning the association between COVID-19 and cancer, are reported. A remaining very debated question regards the use of an innovative class of anti-cancer molecules, the immune checkpoint inhibitors (ICIs), given their modulating effects on the immune system. For that reason, administration of ICIs to cancer patients represents a question mark during this pandemic, as its correlation with COVID-19-associated risks is still under investigation. Based on the mechanisms of action of ICIs and the current evidence, we suggest that ICIs not only can be safely administered to cancer patients, but they might even be beneficial in COVID-19-positive cancer patients, by exerting an immune-stimulating action.

scholarly journals Association of Steroids Use with Survival in Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 546 ◽  
Author(s):  
Fausto Petrelli ◽  
Diego Signorelli ◽  
Michele Ghidini ◽  
Antonio Ghidini ◽  
Elio Gregory Pizzutilo ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Symptom Control ◽  
Cochrane Library ◽  
Risk Of Death ◽  
Increased Risk

Immune checkpoint inhibitors (ICIs) can elicit toxicities by inhibiting negative regulators of adaptive immunity. Sometimes, management of toxicities may require systemic glucocorticoids. We performed a systematic review and meta-analysis of published studies to evaluate the correlation between steroids use, overall survival (OS), and progression-free survival (PFS) in cancer patients treated with ICIs. Publications that compared steroids with non-steroid users in cancer patients treated with ICIs from inception to June 2019 were identified by searching the EMBASE, PubMed, SCOPUS, Web of Science, and Cochrane Library databases. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Patients (studies, n = 16; patients, n = 4045) taking steroids were at increased risk of death and progression compared to those not taking steroids (HR = 1.54, 95% CI: 1.24–1.91; p = 0.01 and HR = 1.34, 95% CI: 1.02–1.76; p = 0.03, respectively). The main negative effect on OS was associated with patients taking steroids for supportive care (HR = 2.5, 95% CI 1.41–4.43; p < 0.01) or brain metastases (HR = 1.51, 95% CI 1.22–1.87; p < 0.01). In contrast, steroids used to mitigate adverse events did not negatively affect OS. In conclusion, caution is needed when steroids are used for symptom control. In these patients, a negative impact of steroid use was observed for both OS and PFS.

Abstract P324: Differences in Incident Diabetes Mellitus and Atherosclerotic Cardiovascular Disease in Chronic Inflammatory Diseases

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Simran Chadha ◽  
Adovich Rivera ◽  
Anna Pawlowski ◽  
Donald M Lloyd-jones ◽  
Matthew J Feinstein
Keyword(s):  
Diabetes Mellitus ◽  
Cardiovascular Disease ◽  
Inflammatory Diseases ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cvd Risk ◽  
Public Insurance ◽  
Chronic Inflammatory Diseases ◽  
Increased Risk ◽  
Male Sex ◽  
Incident Cases

Introduction: Several chronic inflammatory diseases (CID) are associated with elevated risks for cardiovascular diseases (CVDs). However, the relative magnitude of elevated CVD risk may differ considerably between chronic inflammatory diseases. Hypothesis: We hypothesized that not all CIDs are associated with elevated risk for diabetes mellitus (DM) and atherosclerotic cardiovascular disease (ASCVD), and that magnitudes of increased CVD risk differ considerably across CIDs. Methods: We estimated the incidence of DM and ASCVD in 18,373 patients with any of six CIDs [human immunodeficiency virus infection (HIV), Irritable bowel disease (IBD), psoriasis, rheumatoid arthritis (RA), scleroderma, and systemic lupus erythematosus (SLE)] in regular outpatient care, as well as controls without CIDs in regular primary care, in a large metropolitan health system since January 1 st , 2000. We assessed incidence of outcomes in patients with each CID compared to controls using quasi-Poisson regression adjusting for age, sex, insurance status, and common CVD risk factors. A 90-day blanking period was applied for identifying incident cases. Results: Psoriasis, HIV, male sex, black race, Hispanic ethnicity, and being on public insurance were all associated with significantly elevated risks for DM (Figure). HIV, RA, scleroderma, SLE, male sex, and public insurance were all associated with significantly elevated risks for ASCVD. The magnitude of increased risk for ASCVD was similarly high for HIV (incidence rate ratio 1.79, 95% confidence interval 1.57-2.05), scleroderma (1.79, 1.42-2.27), and SLE (1.95, 1.59-2.39). Conclusion: Several, but not all, CIDs are associated with elevated risks for DM and ASCVD, but the magnitude of risk elevation differs depending on the CID. These data demonstrate the importance of nuanced approaches to understanding CID- and inflammation-associated CVD risks.

scholarly journals Cancer and Immune Checkpoint Inhibitor Treatment in the Era of SARS-CoV-2 Infection

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3383
Author(s):  
Thilo Gambichler ◽  
Judith Reuther ◽  
Christina H. Scheel ◽  
Laura Susok ◽  
Peter Kern ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Viral Infections ◽  
Checkpoint Inhibitors ◽  
Severe Infection ◽  
Increased Risk ◽  
Anti Cancer ◽  
The Right ◽  
Inhibitor Treatment

Whether cancer patients receiving immune checkpoint inhibitors (ICI) are at an increased risk of severe infection and mortality during the corona pandemic is a hotly debated topic that will continue to evolve. Here, we summarize and discuss current studies regarding COVID-19 and anti-cancer treatment with an emphasis on ICI. Importantly, several lines of evidence suggest that patients currently treated with ICI do not display an increased vulnerability to infection with SARS-CoV-2. Data regarding morbidity and mortality associated with COVID-19 in cancer patients receiving ICI are less clear and often conflicting. Although mostly based on experimental data, it is possible that ICI can promote the exacerbated immune response associated with adverse outcome in COVID-19 patients. On the other hand, mounting evidence suggests that ICI might even be useful in the treatment of viral infections by preventing or ameliorating T cell exhaustion. In this context, the right timing of treatment might be essential. Nevertheless, some cancer patients treated with ICI experience autoimmune-related side effects that require the use of immunosuppressive therapies, which in turn may promote a severe course of infection with SARS-CoV-2. Although there is clear evidence that withholding ICI will have more serious consequences, further studies are urgently needed in to better evaluate the effects of ICI in patients with COVID-19 and the use of ICI during the corona pandemic in general.

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