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.

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 Immune-related adverse events with immune checkpoint inhibitors affecting the skeleton: a seminal case series

2018 ◽  
Vol 6 (1) ◽  
Author(s):  
Kendall F. Moseley ◽  
Jarushka Naidoo ◽  
Clifton O. Bingham ◽  
Michael A. Carducci ◽  
Patrick M. Forde ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Series

scholarly journals FRI0591 RHEUMATIC IMMUNE-RELATED ADVERSE EVENTS ASSOCIATED WITH TREATMENT WITH IMMUNE CHECKPOINT INHIBITORS: A CASE SERIES FROM TWO REFERRAL CENTRES

2019 ◽  
Author(s):  
Sebastian C. Rodriguez-García ◽  
David Lobo ◽  
Raul Castellanos-Moreira ◽  
Millán Arciniegas Ana Milena ◽  
Roberto Gumucio ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Series

scholarly journals Immune checkpoint inhibitor-induced aseptic meningitis and encephalitis: a case-series and narrative review

2021 ◽  
Vol 12 ◽  
pp. 204209862110047
Author(s):  
Laure Thouvenin ◽  
Timothée Olivier ◽  
Giuseppe Banna ◽  
Alfredo Addeo ◽  
Alex Friedlaender
Keyword(s):  
Adverse Events ◽  
Aseptic Meningitis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Case Series ◽  
Plain Language ◽  
Wide Range

Background: Along with the increasing use of immune checkpoint inhibitors comes a surge in immune-related toxicity. Here, we review the currently available data regarding neurological immune adverse events, and more specifically aseptic meningitis and encephalitis, and present treatment and diagnostic recommendations. Furthermore, we present five cases of immunotherapy-induced aseptic meningitis and encephalitis treated at our institution. Recent findings: Neurological immune-related adverse events, including aseptic meningitis and encephalitis, secondary to checkpoint inhibitors are a rare but complex and clinically relevant entity, comprising a wide range of diseases, most often presenting with symptoms with a wide range of differential diagnoses. Our case-series highlights the challenges of such entities and the importance of properly identifying and managing aseptic meningitis and encephalitis. Summary: Checkpoint inhibitor-induced meningoencephalitis warrants prompt investigations and treatment. Properly diagnosing aseptic meningitis, encephalitis, or mixed presentations may guide the treatment decision, as highlighted by our case-series. After rapid exclusion of alternative diagnoses, urgent corticosteroids are the therapeutic backbone but this could change in favour of highly specific cytokine-directed treatment options. Plain language summary Aseptic meningitis and encephalitis with immune checkpoint inhibitors: a single centre case-series and review of the literature Over the course of the past decade, checkpoint inhibitors have revolutionized cancer care. With their favourable toxicity profile and potential for durable and deep responses, they have become ubiquitous across the field of oncology. Furthermore, combination checkpoint inhibitors are also gaining ground, with increased efficacy and, unfortunately, immune-related toxicity. While there are guidelines based on extensive clinical experience for frequent adverse events, uncommon entities are less readily identified and treated. Neurological immune-related adverse events secondary to checkpoint inhibitors are a rare but complex entity, comprising a wide range of diseases, most often presenting with aspecific symptoms. In this paper, we discuss a single institution case-series of patients with autoimmune aseptic meningitis and encephalitis, and we perform a narrative literature review on this subject. We conclude with our treatment recommendations based on available evidence.

Myasthenia gravis and Guillain-Barré syndrome adverse events with immune checkpoint inhibitors.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 37-37 ◽  
Author(s):  
Catherine R. Garcia ◽  
Jessica N Cox ◽  
John L. Villano
Keyword(s):  
Adverse Events ◽  
Myasthenia Gravis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Guillain Barre Syndrome ◽  
Ocular Myasthenia ◽  
Guillain Barré Syndrome ◽  
Myasthenic Syndrome ◽  
Guillain Barré

37 Background: Immune checkpoint inhibitors (ICI) have provided landmark breakthrough achieving success in prolonging survival in multiple cancer types. As a new class of therapy immune related serious adverse drug reactions (sADRs) have had limited reporting. This includes neurologic based, with reports limited to clinical trials and case-based. Ours is the largest database analysis to date reporting neurological adverse events after ICI therapy. Methods: We analyzed the FDA Adverse Event Reporting System (FAERS) database for pembrolizumab, atezolizumab, nivolumab, and ipilimumab two years prior their FDA approval to September 2017, to include all cases reported with Guillain-Barré syndrome (GBS), Myasthenia gravis, ocular myasthenia, and myasthenic syndrome after the usage of ICI. Results: A total 35,726 cases were reported in FAERS. We identified a total of 263 cases of which 121 (46%) were GBS, 112 (42.6%) myasthenia gravis, 22 myasthenic syndrome (8.4%), and 8 (3%) ocular myasthenia. The mean age in our study was 66 years, with 63% being male. The majority of the cases were reported in the United States (49%), followed by Japan (10%), France (6%), and Australia (5.7%). Over 30% of patients presented more than one significant symptom. Around 20% of these patients were taking more than one immune checkpoint inhibitor, combining ipilimumab with either nivolumab or pembrolizumab. A significantly higher proportion of patients with GBS taking more than one ICI (28.1%, p = 0.013). Nivolumab was the most common ICI in patients with myasthenia gravis, myasthenic syndrome, and ocular myasthenia, while ipilimumab was the most common in patients with GBS. Sixty four percent of these patients required hospitalization, 17% were reported as life threatening events, 7% resulted in disability, and 22% died. Conclusions: Neurological adverse events associated with ICI are relatively uncommon, but can have serious clinical consequences. Recognizing and detailing neurological immune syndromes in relation to ICI therapy are essential in the oncological and neurological practice due to the growing usage of these agents in cancer treatment.

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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