scholarly journals Frequency and distribution of various rheumatic disorders associated with checkpoint inhibitor therapy

Rheumatology ◽  
2019 ◽  
Vol 58 (Supplement_7) ◽  
pp. vii40-vii48 ◽  
Author(s):  
Noha Abdel-Wahab ◽  
Maria E Suarez-Almazor
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Incidence Rates ◽  
Cancer Therapies ◽  
True Incidence ◽  
Immune System Activation ◽  
Treatment Paradigm ◽  
Checkpoint Inhibitor Therapy ◽  
Prospective Longitudinal

Abstract Immune checkpoint inhibitors have advanced the treatment paradigm of various cancers, achieving remarkable survival benefits. However, a myriad of immune-related adverse events (irAE) has been recognized in almost every organ system, presumably because of persistent immune system activation. Rheumatic symptoms such as arthralgia or myalgia are very common. More specific irAE are increasingly being reported. The most frequent ones are inflammatory arthritis, polymyalgia-like syndromes, myositis and sicca manifestations. These rheumatic irAE can develop in ∼5–10% of patients treated with immune checkpoint inhibitors, although true incidence rates cannot be estimated given the lack of prospective cohort studies, and likely underreporting of rheumatic irAE in oncology trials. In this review, we will provide a summary of the epidemiologic data reported for these rheumatic irAE, until more robust prospective longitudinal studies become available to further define the true incidence rate of rheumatic irAE in patients receiving these novel cancer therapies.

scholarly journals A new biological triangle in cancer: intestinal microbiota, immune checkpoint inhibitors and antibiotics

2021 ◽  
Author(s):  
Jie Zhang ◽  
Zhujiang Dai ◽  
Cheng Yan ◽  
Wenjie Zhang ◽  
Daorong Wang ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Epidemiological Studies ◽  
Term Survival ◽  
Checkpoint Inhibitor Therapy ◽  
Rational Use Of Antibiotics

AbstractCancer immunotherapy has revolutionized the treatment of many malignant tumors. Although immune checkpoint inhibitors (ICIs) can reactivate the anti-tumor activity of immune cells, sensitivity to immune checkpoint inhibitor therapy depends on the complex tumor immune processes. In recent years, numerous researches have demonstrated the role of intestinal microbiota in immunity and metabolism of the tumor microenvironment, as well as the efficacy of immunotherapy. Epidemiological studies have further demonstrated the efficacy of antibiotic therapy on the probability of patients' response to ICIs and predictability of the short-term survival of cancer patients. Disturbance to the intestinal microbiota significantly affects ICIs-mediated immune reconstitution and is considered a possible mechanism underlying the development of adverse effects during antibiotic-based ICIs treatment. Intestinal microbiota, antibiotics, and ICIs have gradually become important considerations for the titer of immunotherapy. In the case of immunotherapy, the rational use of antibiotics and intestinal microbiota is expected to yield a better prognosis for patients with malignant tumors.

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.

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.

A Career in Lung Cancer: Pushing Beyond Chemotherapy

2019 ◽  
pp. 583-589
Author(s):  
Pradnya Dinkar Patil ◽  
Frances Shepherd ◽  
David H. Johnson
Keyword(s):  
Lung Cancer ◽  
Targeted Therapies ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Acquired Resistance ◽  
Genetic Alterations ◽  
Disease Biology ◽  
Formidable Challenge ◽  
Treatment Paradigm

The landscape of treatments for non–small cell lung cancer (NSCLC) has evolved dramatically over the past 3 decades. A better understanding of the disease biology and identification of actionable genetic alterations heralded an era of targeted therapies that has led to unprecedented survival benefits in patients with oncogene-driven NSCLC. More recent breakthroughs in immunotherapy led to the development of immune checkpoint inhibitors that have changed the treatment paradigm for patients with advanced NSCLC because of their ability to produce durable responses, resulting in improved survival outcomes. Despite the unparalleled success of these agents, primary and acquired resistance to these therapies pose a formidable challenge. In this article, we provide an overview of the therapeutic advances in the treatment of NSCLC, mechanisms of resistance, and potential strategies to overcome resistance to targeted therapies and immune checkpoint inhibitors.

scholarly journals Immunosurveillance and Immunoediting of Lung Cancer: Current Perspectives and Challenges

2020 ◽  
Vol 21 (2) ◽  
pp. 597 ◽  
Author(s):  
Kei Kunimasa ◽  
Taichiro Goto
Keyword(s):  
Lung Cancer ◽  
Immune System ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Tumor Evolution ◽  
Clinical Activity ◽  
Cancer Immunoediting ◽  
Treatment Paradigm ◽  
Nsclc Patients

The immune system plays a dual role in tumor evolution—it can identify and control nascent tumor cells in a process called immunosurveillance and can promote tumor progression through immunosuppression via various mechanisms. Thus, bilateral host-protective and tumor-promoting actions of immunity are integrated as cancer immunoediting. In this decade, immune checkpoint inhibitors, specifically programmed cell death 1 (PD-1) pathway inhibitors, have changed the treatment paradigm of advanced non-small cell lung cancer (NSCLC). These agents are approved for the treatment of patients with NSCLC and demonstrate impressive clinical activity and durable responses in some patients. However, for many NSCLC patients, the efficacy of immune checkpoint inhibitors is limited. To optimize the full utility of the immune system for eradicating cancer, a broader understanding of cancer immunosurveillance and immunoediting is essential. In this review, we discuss the fundamental knowledge of the phenomena and provide an overview of the next-generation immunotherapies in the pipeline.

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 Immune Checkpoint Inhibitor Therapy for Bone Metastases: Specific Microenvironment and Current Situation

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Chang Liu ◽  
Miao Wang ◽  
Changli Xu ◽  
Bo Li ◽  
Juxiang Chen ◽  
...  
Keyword(s):  
Bone Metastasis ◽  
Bone Metastases ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Basic Research ◽  
Research Progress ◽  
Immunological Mechanism ◽  
Carcinoma Prostate ◽  
Checkpoint Inhibitor Therapy

The treatment of bone metastases is a thorny issue. Immunotherapy may be one of the few hopes for patients with unresectable bone metastases. Immune checkpoint inhibitors are the most commonly used immunotherapy drugs currently. In this review, the characteristics and interaction of bone metastases and their immune microenvironment were systematically discussed, and the relevant research progress of the immunological mechanism of tumor bone metastasis was reviewed. On this basis, we expounded the clinical application of immune checkpoint inhibitors for bone metastasis of common tumors, including non-small-cell lung cancer, renal cell carcinoma, prostate cancer, melanoma, and breast cancer. Then, the deficiencies and limitations in current researches were summarized. In-depth basic research on bone metastases and optimization of clinical treatment is needed.

scholarly journals Proposed diagnostic and treatment paradigm for high-grade neurological complications of immune checkpoint inhibitors

2018 ◽  
Vol 6 (5) ◽  
pp. 340-345 ◽  
Author(s):  
Dustin Anderson ◽  
Grayson Beecher ◽  
Nabeela Nathoo ◽  
Michael Smylie ◽  
Jennifer A McCombe ◽  
...  
Keyword(s):  
Nervous System ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Neurological Complications ◽  
High Grade ◽  
Small Cell Lung ◽  
Cytotoxic Lymphocyte ◽  
Programmed Cell Death 1 ◽  
Treatment Paradigm

Abstract Immune checkpoint inhibitors such as antibodies to cytotoxic lymphocyte-associated protein 4 (ipilimumab) and programmed cell-death 1 (pembrolizumab, nivolumab) molecules have been used in non-small cell lung cancer, metastatic melanoma, and renal-cell carcinoma, among others. With these agents, immune-related adverse events (irAEs) can occur, including those affecting the neurological axis. In this review, high-grade neurological irAEs associated with immune checkpoint inhibitors including cases of Guillain-Barré syndrome (GBS) and myasthenia gravis (MG) are analyzed. Based on current literature and experience at our institution with 4 cases of high-grade neurological irAEs associated with immune checkpoint inhibitors (2 cases of GBS, 1 case of meningo-radiculitis, and 1 case of myelitis), we propose an algorithm for the investigation and treatment of high-grade neurological irAEs. Our algorithm incorporates both peripheral nervous system (meningo-radiculitis, GBS, MG) and central nervous system presentations (myelitis, encephalopathy). It is anticipated that our algorithm will be useful both to oncologists and neurologists who are likely to encounter neurological irAEs more frequently in the future as immune checkpoint inhibitors become more widely used.

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