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 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 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 Unusual Adverse Effects of Immune Checkpoint Inhibitors: Autonomic Neuropathy, Palmoplantar Keratoderma, Reiter Syndrome & Myasthenia Gravis: A Case Series and Review of the Literature

2020 ◽  
Vol 5 (11) ◽  
pp. 554-560
Author(s):  
Walid Shalata ◽  
Alexander Yakobson ◽  
Ismaell Massalha ◽  
Aharon Y. Cohen ◽  
Iris M. Goldstein ◽  
...  
Keyword(s):  
Adverse Events ◽  
Myasthenia Gravis ◽  
Lung Adenocarcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Series ◽  
Palmoplantar Keratoderma ◽  
Stage 4 ◽  
Reiter Syndrome

The immune checkpoint inhibitors (ICIs) have transformed the standards of care in cancer treatment and has dramatically improved patient prognoses. As a result of the introduction of these novel treatments several types of adverse events related to ICIs (immune related adverse events ((irAEs)) have been observed and reported. In this case series we describe the clinical course of four patients, with unusual ICI induced toxicities. The first patient was a 59 year-old female who received chemo-immunotherapy (pembrolizumab) for stage 4- lung adenocarcinoma, and developed autonomic neuropathy (AN). The second and third patients were both 63 year-old males who also received chemo-immunotherapy (pembrolizumab) for stage 4-A lung adenocarcinoma. One of those patients developed palmoplantar keratoderma and one developed conjunctivitis, urethritis and arthritis (Reiter syndrome). The fourth patient was an 80 year-old male who received chemo-immunotherapy (pembrolizumab) for stage 3-A squamous cell carcinoma of the lung and developed myasthenia gravis.

Incidence of Immune Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitors, Case Series from Two Tertiary Care Centeers in Dubai, UAE

2020 ◽  
Vol 106 (1_suppl) ◽  
pp. 25-25
Author(s):  
M Omara ◽  
Elamin Abdelgadir ◽  
F Khan ◽  
M F Latif ◽  
Fatheya Alawadi ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Thyroid Dysfunction ◽  
Checkpoint Inhibitors ◽  
Cancer Type ◽  
American Hospital ◽  
Advanced Malignancy ◽  
Grade Ii ◽  
Grade Iii

Introduction: Immune checkpoint inhibitors (ICI) represent a major component of systemic therapy in advanced malignancy. Studies have reported unique spectrum of toxicity profile of ICI as compared to systemic chemotherapy. Aim of this study is to evaluate toxicities of ICI in our population and to compare this with published data. Material and Methods: We retrospectively reviewed medical records of patients treated with ICI at Dubai hospital and American hospital Dubai from November 2015 to April 2019. After patient identification from hospitals cancer registry, data regarding patients’ demographics, cancer type, type of ICI, adverse events, and duration of treatment were collected. Results: Forty-Five patients were identified with median age of 60 (27-80) years. 27 (60%) patients were male and 18 (40%) were female. Underlying diagnosis was lung cancer (n=25), renal cell cancer (n=6), melanoma (n=5), bladder cancer (n=3), Hodgkins lymphoma (n=3) and other malignancies (n=3). Majority of patients received Nivolumab (n=20, 44%) followed by Pembrolizumab (n=19, 42%), Atezolizumab (n=4, 9%) and Durvalumab (n=2, 5%) respectively. Thyroid dysfunction was the most common side effect observed in 17 (38%) patients including hypothyroidism (n=12, 27%) and hyperthyroidism (n=5, 11%). 53 % patients treated with Nivolumab developed thyroid dysfunction as compared to Pembrolizumab (22%). 7 patients (16%) had elevated liver enzymes. Grade II and III hepatotoxicity was noted in 1 patient (2.2 %) each. One patient (2.2 %) developed grade II skin toxicity. One patient (2.2 %) developed grade III colitis. Grade II, III and IV pneumonitis was observed in 2 (4.4 %), 1 (2.2%) and 1 (2.2%) patient respectively. Immune mediated adverse events were managed according to standard guidelines and 2 patients (4.4 %) had treatment discontinuation due to grade IV Pneumonitis and grade III Colitis. Conclusion: Our study reports relatively higher incidence of thyroid adverse events in patients treated with ICI. The incidence of grade III-IV immune related toxicity remains low. Overall treatment with ICI was tolerated reasonably well and toxicity was manageable.

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 IMMU-04. IMMUNE-RELATED ADVERSE EVENTS STRONGLY PREDICT SUPERIOR OUTCOMES IN BRAIN METASTASES PATIENTS RECEIVING LOCAL TREATMENT AND IMMUNE CHECKPOINT INHIBITORS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii105-ii105
Author(s):  
Alexander Hulsbergen ◽  
Asad Lak ◽  
Yu Tung Lo ◽  
Nayan Lamba ◽  
Steven Nagtegaal ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Adverse Events ◽  
Brain Metastases ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Local Treatment ◽  
Sensitivity Analyses ◽  
Immortal Time Bias ◽  
The Brain

Abstract INTRODUCTION In several cancers treated with immune checkpoint inhibitors (ICIs), a remarkable association between the occurrence of immune-related adverse events (irAEs) and superior oncological outcomes has been reported. This effect has hitherto not been reported in the brain. This study aimed to investigate the relation between irAEs and outcomes in brain metastases (BM) patients treated with both local treatment to the brain (LT; i.e. surgery and/or radiation) and ICIs. METHODS This study is a retrospective cohort analysis of patients treated for non-small cell lung cancer (NSCLC) BMs in a tertiary institution in Boston, MA. Outcomes of interest were overall survival (OS) and intracranial progression-free survival (IC-PFS), measured from the time of LT. Sensitivity analyses were performed to account for immortal time bias (i.e., patients who live longer receive more cycles of ICIs and thus have more opportunity to develop an irAE). RESULTS A total of 184 patients were included; 62 (33.7%) were treated with neurosurgical resection and 122 (66.3%) with upfront brain radiation. irAEs occurred in 62 patients (33.7%). After adjusting for lung-Graded Prognostic Assessment, type of LT, type of ICI, newly diagnosed vs. recurrent BM, BM size and number, targetable mutations, and smoking status, irAEs were strongly associated with better OS (HR 0.33, 95% CI 0.19 – 0.58, p < 0.0001) and IC-PFS (HR 0.41; 95% CI 0.26 – 0.65; p = 0.0001). Landmark analysis including only patients who received more than 3 cycles of ICI (n = 133) demonstrated similar results for OS and IC-PFS, as did sensitivity analysis adjusting for the number of cycles administered (HR range 0.36 – 0.51, all p-values < 0.02). CONCLUSIONS After adjusting for known prognostic factors, irAEs strongly predict superior outcomes after LT in NSCLC BM patients. Sensitivity analysis suggests that this is unlikely due to immortal time bias.

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