scholarly journals Mechanisms of immune-related adverse events during the treatment of cancer with immune checkpoint inhibitors

Rheumatology ◽  
2019 ◽  
Vol 58 (Supplement_7) ◽  
pp. vii59-vii67 ◽  
Author(s):  
Sophia C Weinmann ◽  
David S Pisetsky
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Immunosuppressive Treatment ◽  
Cell Repertoire ◽  
Autoantibody Production ◽  
Rheumatic Manifestations ◽  
Checkpoint Inhibitor Therapy

AbstractImmune checkpoint inhibitors are novel biologic agents to treat cancer by inhibiting the regulatory interactions that limit T cell cytotoxicity to tumours. Current agents target either CTLA-4 or the PD-1/PD-L1 axis. Because checkpoints may also regulate autoreactivity, immune checkpoint inhibitor therapy is complicated by side effects known as immune-related adverse events (irAEs). The aim of this article is to review the mechanisms of these events. irAEs can involve different tissues and include arthritis and other rheumatic manifestations. The frequency of irAEs is related to the checkpoint inhibited, with the combination of agents more toxic. Because of their severity, irAEs can limit therapy and require immunosuppressive treatment. The mechanisms leading to irAEs are likely similar to those promoting anti-tumour responses and involve expansion of the T cell repertoire; furthermore, immune checkpoint inhibitors can affect B cell responses and induce autoantibody production. Better understanding of the mechanisms of irAEs will be important to improve patient outcome as well as quality of life during treatment.

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.

Autoimmune encephalitis associated with Ma2 antibodies and immune checkpoint inhibitor therapy

2020 ◽  
Vol 20 (3) ◽  
pp. 256-259 ◽  
Author(s):  
Shane Lyons ◽  
Ronan Joyce ◽  
Patrick Moynagh ◽  
Luke O'Donnell ◽  
Silive Blazkova ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Autoimmune Encephalitis ◽  
Advanced Malignancy ◽  
Temporal Lobes ◽  
Stage 4 ◽  
Fluid Attenuated Inversion Recovery ◽  
Checkpoint Inhibitor Therapy

Immune checkpoint inhibitors have transformed the treatment of advanced malignancy, while increasing the risk of immune-related adverse events. A 56-year-old woman who had received nivolumab for stage 4 renal cell carcinoma subsequently developed altered behaviour, memory deficits and worsening of previously stable epilepsy. MR scan of the brain showed bilateral FLAIR (fluid-attenuated inversion recovery) hyperintensity of the mesial temporal lobes, and there were anti-Ma2 antibodies in both serum and cerebrospinal fluid. She was treated with corticosteroids but developed further clinical relapses requiring immunoglobulin and rituximab. The immune-related adverse events relating to immune checkpoint inhibitors are an emerging challenge for the neurologist. Some cases are refractory and require serial immunosuppression.

scholarly journals Gastrointestinal adverse events associated with immune checkpoint inhibitor therapy

2019 ◽  
Vol 8 (1) ◽  
pp. 25-30 ◽  
Author(s):  
Eva Rajha ◽  
Patrick Chaftari ◽  
Mona Kamal ◽  
Julian Maamari ◽  
Christopher Chaftari ◽  
...  
Keyword(s):  
Adverse Events ◽  
Health Care Providers ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Care Providers ◽  
Organ Systems ◽  
Checkpoint Inhibitor Therapy ◽  
Recent Addition ◽  
Gastrointestinal Adverse Events

Abstract Immunotherapy with checkpoint inhibitors has revolutionized cancer therapy and is now the standard treatment for several different types of cancer, supported by favorable outcomes and good tolerance. However, it is linked to multiple immune manifestations, referred to as immune-related adverse events (irAEs). These adverse events frequently affect the skin, colon, endocrine glands, lungs, and liver. The gastrointestinal system is one of the most commonly affected organ systems and is responsible for the most frequent emergency visits resulting from irAEs. However, because immune checkpoint inhibitors are a recent addition to our arsenal of cancer drugs, many health-care providers remain unfamiliar with the management of irAEs. Gastroenterologists involved in the treatment of oncology patients who have received checkpoint inhibitors are currently encountering cases of abdominal pain, diarrhea, and other nonspecific symptoms that may be challenging to manage. This article reviews the gastrointestinal, hepatic, and pancreatic toxicities of checkpoint inhibitors and provides an approach to their diagnosis and recommended workup. It also highlights the management of irAEs according to their toxicity grading and specifically discusses the instances in which corticosteroids should be administered and/or the immune checkpoint inhibitors should be withheld.

scholarly journals Immune Checkpoint Inhibitors Mediated Lymphocytic and Giant Cell Myocarditis: Uncovering Etiological Mechanisms

2021 ◽  
Vol 8 ◽  
Author(s):  
Rishi Rikhi ◽  
Jaret Karnuta ◽  
Muzna Hussain ◽  
Patrick Collier ◽  
Pauline Funchain ◽  
...  
Keyword(s):  
T Cell ◽  
Giant Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Immunosuppressive Treatment ◽  
Cell Infiltrate ◽  
Giant Cell Myocarditis ◽  
Lymphocytic Myocarditis

The advent of immune checkpoint inhibitors (ICIs) has revolutionized the field of oncology, but these are associated with immune related adverse events. One such adverse event, is myocarditis, which has limited the continued immunosuppressive treatment options in patients afflicted by the disease. Pre-clinical and clinical data have found that specific ICI targets and precipitate distinct myocardial infiltrates, consistent with lymphocytic or giant cell myocarditis. Specifically, it has been reported that CTLA-4 inhibition preferentially results in giant cell myocarditis with a predominately CD4+ T cell infiltrate and PD-1 inhibition leads to lymphocytic myocarditis, with a predominately CD8+ T cell infiltrate. Our manuscript discusses the latest literature surrounding ICI pathways and targets, while detailing proposed mechanisms behind ICI mediated myocarditis.

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 Immune-related adverse events caused by combined immune checkpoint inhibitor therapy with nivolumab and ipilimumab for lung cancer

2022 ◽  
Vol 6 (1) ◽  
Author(s):  
Takashi Nomizo ◽  
Haruka Yamamoto ◽  
Tsunetaka Murayama ◽  
Hiroko Fukata ◽  
Yasukiyo Nakamura ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Therapeutic Effects ◽  
Skin Injury ◽  
Checkpoint Inhibitor Therapy ◽  
Grade 3

It has been less than a decade since immune checkpoint inhibitors became the mainstay of lung cancer treatment, and 2020 saw the advent of the era of complex immune checkpoint inhibitors. Although clinical trials have shown that the therapeutic effects of complex immune checkpoint inhibitors are favorable, they are associated with an increase in adverse events. The use of combined immune checkpoint inhibitors in clinical practice has progressed slowly, and the frequency and types of adverse events they cause remain unclear. Here we report the adverse events of six patients with lung cancer treated with regimens containing nivolumab and ipilimumab in 2021. Four of the six patients had grade 3 or higher adverse events, including one patient with lung injury and one patient with skin injury, both of whom died. The timing and nature of the adverse events were difficult to predict.

scholarly journals Rheumatic Manifestations and Diseases From Immune Checkpoint Inhibitors in Cancer Immunotherapy

2021 ◽  
Vol 8 ◽  
Author(s):  
Pan Shen ◽  
Xuan Deng ◽  
Zhishuo Hu ◽  
Zhe Chen ◽  
Yao Huang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Rheumatic Diseases ◽  
Lupus Erythematosus ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Clinical Manifestations ◽  
Multidisciplinary Cooperation ◽  
Rheumatic Manifestations ◽  
Underlying Mechanisms

Immune checkpoint inhibitors (ICIs), which can enhance antitumor immunity and inhibit cancer growth, have revolutionized the treatment of multiple cancers and dramatically decreased mortality. However, treatment with ICIs is directly associated with immune-related adverse events (irAEs) because of inflammation in off-target organs and autoimmunity resulting from non-specific immune activation. These irAEs can cause rheumatic diseases and manifestations such as inflammatory arthritis, polymyalgia rheumatica, myositis, vasculitis, Sicca and Sjogen's syndrome, and systemic lupus erythematosus. Early diagnosis and treatment of these adverse events will improve outcomes and quality of life for cancer patients. The treatment of rheumatic diseases induced by ICIs requires multidisciplinary cooperation among physicians. Furthermore, the underlying mechanisms are not fully understood and it is difficult to predict and evaluate these side effects precisely. In this review, we summarize available studies and findings about rheumatic irAEs, focusing mainly on the clinical manifestations, epidemiology, possible mechanisms, and guiding principles for treating these irAEs.

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