Immune checkpoint inhibitors in the management of malignancies in transplant recipients

2018 ◽  
Vol 94 (1118) ◽  
pp. 704-708 ◽  
Author(s):  
Dileep Kumar Reddy Regalla ◽  
Grant R Williams ◽  
Ravi kumar Paluri
Keyword(s):  
Monoclonal Antibodies ◽  
Cancer Immunotherapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Transplant Rejection ◽  
Treatment Strategies ◽  
Therapeutic Benefit ◽  
History Of ◽  
Active Research

Cancer immunotherapy, an area of active research, has thus far yielded several exciting breakthroughs in cancer treatment strategies. So far, immune checkpoint inhibitors have been the most promising method of cancer immunotherapy. CTLA-4, PD-1 and PD-L1 are the immune checkpoint molecules against which monoclonal antibodies act against and revolutionised the treatment of several malignancies. However, it is still unclear whether using these monoclonal antibodies in patients with malignancy and a history of transplant is as beneficial as in patients without a history of transplantation. The reason being, with the therapeutic benefit, also comes the inherent disadvantage of transplant rejection because of the activation of T-cells against donor antigens. So, transplant-related complications limit the usage of the checkpoint blockade therapy to treat malignancies. Here, we review the data published in this context and suggest optimal approaches to using the currently available repertoire of immunotherapies.

Cancer Immunotherapy-Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

2021 ◽  
Vol 16 ◽  
Author(s):  
Jing Bai ◽  
Ping Liang ◽  
Qian Li ◽  
Rui Feng ◽  
Jiang Liu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cancer Immunotherapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Locoregional Therapy ◽  
Incidence And Mortality

: Hepatocellular Carcinoma (HCC) is one of the most common malignancies, the incidence and mortality of which are increasing worldwide. Cancer immunotherapy has revolutionized cancer treatment in recent years. In particular, Immune Checkpoint Inhibitors (ICIs) as new therapeutic tools have demonstrated encouraging antitumor activity and manageable tolerability in HCC. Immunologic checkpoint blockade with antibodies targeting Programmed cell Death-1 (PD-1), Programmed cell Death Ligand-1 (PD-L1), and Cytotoxic T Lymphocyte-Associated protein-4 (CTLA-4) strengthens tumor immunity by restoring exhausted T cells. Although the efficacy of combination treatment strategies using ICIs combined with other ICIs, molecular targeted agents, systemic therapy, or locoregional therapy has been well documented in numerous preclinical and clinical studies on several types of cancers, most HCC patients do not benefit from ICI treatment. This review highlights recent developments and potential opportunities related to ICIs and their combination in the management of HCC. The present article also includes recent patent review coverage on this topic.

Atezolizumab-induced myositis and myocarditis in a patient with metastatic urothelial carcinoma

2020 ◽  
Vol 13 (12) ◽  
pp. e236357
Author(s):  
Mary Sessums ◽  
Siva Yarrarapu ◽  
Pramod K Guru ◽  
Devang K Sanghavi
Keyword(s):  
Urothelial Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Basic Knowledge ◽  
Malignant Neoplasms ◽  
Diverse Range ◽  
History Of ◽  
Metastatic Urothelial Carcinoma ◽  
Acute Hypercapnic Respiratory Failure

Immune checkpoint inhibitors have revolutionised cancer therapy in the past decade. Although they have been indicated to treat a diverse range of malignant neoplasms, they are also associated with various immune-related adverse effects. We report the case of a 74-year-old man with a history of urothelial carcinoma who had atezolizumab-induced myocarditis and myositis resulting in acute hypercapnic respiratory failure, despite the discontinuation of atezolizumab and aggressive treatment with corticosteroids. This case highlights the importance of a multidisciplinary approach for early diagnosis and treatment of immune-related adverse events. Physicians must be aware of the risks associated with immune checkpoint inhibitors and have a basic knowledge regarding their management.

scholarly journals Recent Progress in Dendritic Cell-Based Cancer Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2495
Author(s):  
Kazuhiko Matsuo ◽  
Osamu Yoshie ◽  
Kosuke Kitahata ◽  
Momo Kamei ◽  
Yuta Hara ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Immune Checkpoint ◽  
Targeted Delivery ◽  
Cancer Vaccines ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Host Immune Responses ◽  
Near Future ◽  
Identification And Characterization

Cancer immunotherapy aims to treat cancer by enhancing cancer-specific host immune responses. Recently, cancer immunotherapy has been attracting much attention because of the successful clinical application of immune checkpoint inhibitors targeting the CTLA-4 and PD-1/PD-L1 pathways. However, although highly effective in some patients, immune checkpoint inhibitors are beneficial only in a limited fraction of patients, possibly because of the lack of enough cancer-specific immune cells, especially CD8+ cytotoxic T-lymphocytes (CTLs), in the host. On the other hand, studies on cancer vaccines, especially DC-based ones, have made significant progress in recent years. In particular, the identification and characterization of cross-presenting DCs have greatly advanced the strategy for the development of effective DC-based vaccines. In this review, we first summarize the surface markers and functional properties of the five major DC subsets. We then describe new approaches to induce antigen-specific CTLs by targeted delivery of antigens to cross-presenting DCs. In this context, the chemokine receptor XCR1 and its ligand XCL1, being selectively expressed by cross-presenting DCs and mainly produced by activated CD8+ T cells, respectively, provide highly promising molecular tools for this purpose. In the near future, CTL-inducing DC-based cancer vaccines may provide a new breakthrough in cancer immunotherapy alone or in combination with immune checkpoint inhibitors.

scholarly journals Treatment of rheumatic immune-related adverse events due to cancer immunotherapy with immune checkpoint inhibitors—is it time for a paradigm shift?

2020 ◽  
Author(s):  
Katerina Chatzidionysiou ◽  
Matina Liapi ◽  
Georgios Tsakonas ◽  
Iva Gunnarsson ◽  
Anca Catrina
Keyword(s):  
Adverse Events ◽  
Cancer Immunotherapy ◽  
Potential Risk ◽  
Immune Checkpoint ◽  
Paradigm Shift ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Current Evidence ◽  
Inadequate Response ◽  
High Efficacy

Abstract Immunotherapy has revolutionized cancer treatment during the last years. Several monoclonal antibodies that are specific for regulatory checkpoint molecules, that is, immune checkpoint inhibitors (ICIs), have been approved and are currently in use for various types of cancer in different lines of treatment. Cancer immunotherapy aims for enhancing the immune response against cancer cells. Despite their high efficacy, ICIs are associated to a new spectrum of adverse events of autoimmune origin, often referred to as immune-related adverse events (irAEs), which limit the utility of these drugs. These irAEs are quite common and can affect almost every organ. The grade of toxicity varies from very mild to life-threatening. The pathophysiological mechanisms behind these events are not fully understood. In this review, we will summarize current evidence specifically regarding the rheumatic irAEs and we will focus on current and future treatment strategies. Treatment guidelines largely support the use of glucocorticoids as first-line therapy, when symptomatic therapy is not efficient, and for more persistent and/or moderate/severe degree of inflammation. Targeted therapies are higher up in the treatment pyramid, after inadequate response to glucocorticoids and conventional, broad immunosuppressive agents, and for severe forms of irAEs. However, preclinical data provide evidence that raise concerns regarding the potential risk of impaired antitumoral effect. This potential risk of glucocorticoids, together with the high efficacy and potential synergistic effect of newer, targeted immunomodulation, such as tumor necrosis factor and interleukin-6 blockade, could support a paradigm shift, where more targeted treatments are considered earlier in the treatment sequence.

scholarly journals Infections due to dysregulated immunity: an emerging complication of cancer immunotherapy

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2021-217260
Author(s):  
Tommaso Morelli ◽  
Kohei Fujita ◽  
Gil Redelman-Sidi ◽  
Paul T Elkington
Keyword(s):  
Immune Response ◽  
Adverse Events ◽  
Cancer Immunotherapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Immunosuppressive Treatment ◽  
Common Side Effect ◽  
Inflammatory Immune Response ◽  
New Framework

Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment. However, immune-related adverse events (irAEs) are a common side effect which can mimic infection. Additionally, treatment of irAEs with corticosteroids and other immunosuppressant agents can lead to opportunistic infection, which we have classed as immunotherapy infections due to immunosuppression. However, emerging reports demonstrate that some infections can be precipitated by ICIs in the absence of immunosuppressive treatment, in contrast to the majority of reported cases. These infections are characterised by a dysregulated inflammatory immune response, and so we propose they are described as immunotherapy infections due to dysregulated immunity. This review summarises the rapidly emerging evidence of these phenomena and proposes a new framework for considering infection in the context of cancer immunotherapy.

scholarly journals Thrombotic Complications Associated with Immune Checkpoint Inhibitors

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4606
Author(s):  
Tzu-Fei Wang ◽  
Alok A. Khorana ◽  
Marc Carrier
Keyword(s):  
Immune Checkpoint ◽  
Arterial Thrombosis ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Relevant Information ◽  
Anticancer Treatment ◽  
Thrombotic Complications ◽  
Associated Risk Factors ◽  
Cancer Associated Thrombosis

Thromboembolism is a common complication in patients with cancer and is associated with significant morbidity and mortality. Anticancer treatment is a known risk factor of cancer-associated thrombosis. Immune checkpoint inhibitors have become a mainstay of treatment in various cancers. Both venous and arterial thrombosis have been increasingly reported as adverse events associated with immune checkpoint inhibitors in recent studies, with a cumulative incidence of venous thrombosis to be 5–8% at 6 months and over 10% at 12 months. Additionally, rates of approximately 1–5% for arterial thrombosis were reported at 12 months. Data also showed an association of thromboembolism with adverse survival. Many pertinent clinical questions in this population deserve further investigation, including the risks of thrombosis associated with immune checkpoint inhibitors as compared to those with traditional systemic therapy, associated risk factors, and the optimal prevention and treatment strategies. In this review, we synthesize data from available literature, provide relevant information for clinicians and potential future directions for research.

Abstract 12563: Retrospective Analysis of Cardiovascular Events With the Use of Immune Checkpoint Inhibitors

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Tushar Tarun ◽  
Brian P Bostick ◽  
Deepa Baswaraj ◽  
Nishchayjit Basra ◽  
Meeshal Khan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Retrospective Analysis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Multiple Organ ◽  
Fulminant Myocarditis ◽  
Organ Systems ◽  
History Of

Introduction: Immune checkpoint inhibitors have emerged as a promising, novel therapy for multiple malignancies. Immune-related adverse reactions pose a serious concern with use of these agents and reportedly involve multiple organ systems, notably cardiotoxicity. Early identification and management of these adverse events is essential in the prevention of morbidity and mortality. Hypothesis: Immune checkpoint inhibitors cause multiple cardiotoxic effects, and patients with prior cardiac history have a higher likelihood of cardiotoxicity. Methods: 1. A retrospective analysis of 150 patients was performed who had received immunotherapy with either the cytotoxic T lymphocyte associated antigen 4 inhibitors (CTLA4) or with the programmed cell death inhibitors (PD1) or programmed death-ligand 1 (PD-L1) inhibitors for a period of two years at a Tertiary health Care from 7/1/2016-6/30/2018. 2. Patients' cardiac diagnoses prior to the initiation of therapy were noted and included, including history of heart failure, coronary artery disease, atrial fibrillation, and sudden cardiac arrest. 3. Patients’ clinic visits and hospitalizations with admitting and discharge diagnosis, electrocardiogram, echocardiogram, troponin T, and NT-proBNP were reviewed. Results: 6% of patients had new onset heart failure (both preserved and reduced), 1.3% had evidence of myocardial infarction, 2% had new atrial fibrillation with rapid ventricular rate, and 0.6% had fulminant myocarditis. Of patients with new cardiac events, 60% had a history of cardiac disease, which was significantly higher than in patients without (p< 0.05). There were no age or sex differences between the groups with and without cardiotoxicity. Conclusion: Immunotherapy with immune checkpoint inhibitors have broadened the horizon for treatment of multiple solid and hematological malignancies. Nonetheless, new adverse effects on multiple organ systems, specifically cardiac involvement, occur with these therapies, which are important and potentially detrimental toxicities. Patients with a history of prior cardiovascular disease have higher likelihood to develop cardiotoxicity.

scholarly journals Risk factors for cancer-associated thrombosis in patients undergoing treatment with immune checkpoint inhibitors

2019 ◽  
Vol 38 (4) ◽  
pp. 1200-1206 ◽  
Author(s):  
Yosuke Ando ◽  
Takahiro Hayashi ◽  
Reiko Sugimoto ◽  
Seira Nishibe ◽  
Kaori Ito ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Heart Disease ◽  
Anticancer Agents ◽  
Immune Checkpoint ◽  
Odds Ratio ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
History Of ◽  
Cancer Associated Thrombosis

SummaryPurpose Anticancer agents are known to increase cancer-associated thrombosis (CAT) onset. CAT onset rate is reported to be 1.92% in cisplatin-based therapy, 6.1% in paclitaxel plus ramucirumab combination therapy, and 11.9% in bevacizumab monotherapy. Because immune checkpoint inhibitors (ICIs) cause a sudden increase in T cell number, an association between administration of these drugs and increase in CAT incidence is likely. However, the extent to which ICI administration affects CAT incidence remains unclear. Further, risk factors for CAT incidence have not yet been identified. The present study investigated CAT incidence and associated risk factors in patients receiving ICI. Methods Patients administered nivolumab or pembrolizumab at Fujita Health University Hospital from April 2017 to March 2018 were enrolled. We collected retrospective data regarding age, sex, cancer type, BMI, medical history, laboratory data at treatment initiation, medications, and computed tomography (CT) interpretations from electronic medical records. Results We identified 122 eligible participants from 135 patients receiving nivolumab or pembrolizumab. Ten patients (8.2%) developed CAT. A history of venous thromboembolism (VTE) or arterial thromboembolism (ATE) was a risk factor for CAT incidence (odds ratio: 6.36, P = 0.039). A history of heart disease may be a risk factor for CAT incidence (odds ratio 6.56, P = 0.052). Significantly higher usage of antiplatelet and anticoagulant therapy was noted in patients who developed CAT (60%) than in those who did not (13.4%, p < 0.01). Conclusion High (8.2%) CAT incidence during ICI administration suggested that ICI is not associated with a lower blood clot risk than other anticancer agents investigated in previous studies. For patients with VTE, ATE, or heart disease history, it is crucial to consider the possibility of CAT even with antiplatelet therapy.

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