Management of rheumatic complications of immune checkpoint inhibitor therapy – an oncological perspective

Steven, Neil; Fisher, Benjamin A

doi:10.1093/rheumatology/kez536

Cited by 26 publications

(18 citation statements)

References 92 publications

(135 reference statements)

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“…However, with the growing use of CPIs, a significant increase in immune‐related adverse effects has emerged. [ 26 ] A potential marker and detection method monitoring dynamic changes of response to immunotherapy play a vital role. At present, variability of PD‐L1 expression in relation to its predictive role has been addressed in tissue biopsies.…”

Section: Resultsmentioning

confidence: 99%

Applying CRISPR/Cas13 to Construct Exosomal PD‐L1 Ultrasensitive Biosensors for Dynamic Monitoring of Tumor Progression in Immunotherapy

Wang

et al. 2020

Advanced Therapeutics

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Programmed cell death receptor 1 (PD-L1) protein on exosomes (exosomal PD-L1) is one of the most promising biomarkers for cancer immunotherapy monitoring. However, current approaches for exosomal PD-L1 detection are poorly sensitive, laborious, and time-consuming. Here, a new method, named Aptamer-RPA-TMA-Cas13a Assay (ARTCA) is established, which enables exosomal PD-L1 to be detected directly in serum with a lower limit of 10 particles mL −1. Mechanistically, using DNA aptamer specifically binding to exosomal PD-L1, the aptamer is amplified twice by recombinase polymerase amplification (RPA) coupled with transcription-mediated amplification (TMA) and simultaneously the TMA products are detected in real-time with CRISPR/Cas13a system. Utilizing ARTCA, PD-L1 levels in circulating exosomes seem to be a reliable marker of PD-L1 expression in tumor tissue. The level of circulating exosomal PD-L1 increases significantly in patients with tumor progression. Ultra-trace detection of serum exosomal PD-L1 by ARTCA provides a potentially convenient way for dynamic monitoring of tumor progression for patients undergoing immunotherapy. These results demonstrate the use of CRISPR-Cas13a for protein detection, and circulating exosomal PD-L1 levels seem to be a reliable marker as well as PD-L1 expression in tumor tissue, opening up new avenues for monitoring tumor progression.

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Section: Resultsmentioning

confidence: 99%

Applying CRISPR/Cas13 to Construct Exosomal PD‐L1 Ultrasensitive Biosensors for Dynamic Monitoring of Tumor Progression in Immunotherapy

Wang

et al. 2020

Advanced Therapeutics

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“…Rheumatological toxicities should be recognized by the oncologist and treated together with the rheumatologist [20]. At each cancer evaluation, patients receiving immunotherapy should be asked if they have joint or muscle pain, morning stiffness, and xerophthalmia/xerostomia, as well as diffuse pain that could suggest fibromyalgia [19].…”

Section: Discussionmentioning

confidence: 99%

“…There were 348 patients receiving immunotherapy and the incidence of rheumatic adverse events was 10.34%. Retrospective case series reported rheumatological adverse events such as arthralgia, arthritis, seronegative arthritis, and myositis, with an incidence of 3.5-13% [19].…”

Section: Methodsmentioning

confidence: 99%

Rheumatological Adverse Events Following Immunotherapy for Cancer

et al. 2022

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Background and Objectives: The occurrence of rheumatological side effects in a patient after receiving immunotherapy for cancer is becoming increasingly common. Oncologists often fail to diagnose and refer affected patients to rheumatologists. This paper presents the various rheumatological adverse events that occur after immunotherapy in patients as well as their treatment and evolution. Materials and Methods: A total of 36 patients were monitored between November 2018 and March 2020. The oncologist monitoring the immunotherapy-treated patients identified the occurrence of musculoskeletal side effects. The grading of toxicities was performed by both the oncologist and the rheumatologist using common terminology criteria for adverse events (CTCAE). Rheumatological treatment was administered, and for some patients, immunotherapy was discontinued. Results: The clinical presentations of the patients varied. Mild side effects (grade 1–2) were reported in a higher proportion than severe side effects (grade 3–5). Therefore, thirty-one patients had mild-to-moderate side effects, and five patients had severe side effects. Adverse reactions occurred, on average, 10 weeks after the initiation of immunotherapy; this indicated that the severity of the toxicity was dose dependent. Patients were treated with NSAIDs or prednisone, depending on the severity of the side effects, and for patients with severe manifestations, immunotherapy was discontinued. The remission of rheumatic manifestations varied depending on the grade of the manifestations. Conclusions: The clinical, biological, and ultrasound presentations of the patients with adverse events followed by cancer treatments differed from classic rheumatological manifestations. Thorough examinations of these patients by both oncologists and rheumatologists are needed in order to correctly diagnose and treat rheumatological adverse events. Multiple studies that include a larger number of participants are needed in order to better understand the pathogenesis and clinical evolution of these patients under different treatment conditions.

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“…Overall, the myositis-myocarditis-myasthenia gravis overlap represents a serious neuromuscular irAE of PD-1 monoantibodies, and are considerably more deleterious compared with their idiopathic counterparts. Meta-analysis shows that myositis, myocarditis and myasthenia gravis account for one fifth of irAE-related death (21). When the neuromuscular triad is present, the disease progression is particularly malignant.…”

Section: Discussionmentioning

confidence: 99%

Case Report: The Neuromusclar Triad of Immune Checkpoint Inhibitors: A Case Report of Myositis, Myocarditis, and Myasthenia Gravis Overlap Following Toripalimab Treatment

Luo

Tang

Zeng

et al. 2021

Front. Cardiovasc. Med.

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The neuromuscular adverse events of immune checkpoint inhibitor (ICI) treatment include myositis, polymyalgia rheumatica, myocarditis, and myasthenia syndrome. We report a 47-year old female presenting with external ophthalmoplegia, generalized muscle weakness, and third-degree atrioventricular block 4 weeks after toripalimab treatment for metastatic thymoma. Creatine kinase was elevated to 25,200 U/l and cardiac troponin I to 2.796 ng/ml. Autoantibody profiling shows positive anti-ryanodine receptor and anti-acetylcholine receptor antibodies and negative myositis specific antibodies. Repetitive nerve stimulation did not reveal decrement of compound muscle action potentials. Pulse methylprednisolone and immunoglobulin infusion, together with temporary pacemaker insertion normalized her muscle enzyme levels and cardiac rhythm. This is the first report of overlaping neuromuscular adverse event of toripalimab.

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Management of rheumatic complications of immune checkpoint inhibitor therapy – an oncological perspective

Cited by 26 publications

References 92 publications

Applying CRISPR/Cas13 to Construct Exosomal PD‐L1 Ultrasensitive Biosensors for Dynamic Monitoring of Tumor Progression in Immunotherapy

Applying CRISPR/Cas13 to Construct Exosomal PD‐L1 Ultrasensitive Biosensors for Dynamic Monitoring of Tumor Progression in Immunotherapy

Rheumatological Adverse Events Following Immunotherapy for Cancer

Case Report: The Neuromusclar Triad of Immune Checkpoint Inhibitors: A Case Report of Myositis, Myocarditis, and Myasthenia Gravis Overlap Following Toripalimab Treatment

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