Prediction of Immune-Related Adverse Events Induced by Immune Checkpoint Inhibitors With a Panel of Autoantibodies: Protocol of a Multicenter, Prospective, Observational Cohort Study. | LitMetric
Osakidetza Basque Health Service, Araba University Hospital, Department of Medical Oncology, Vitoria-Gasteiz, Spain.
Published: June 2022
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Article Abstract
Immune checkpoint inhibitor (ICI) therapy is markedly improving the prognosis of patients with several types of cancer. On the other hand, the growth in the use of these drugs in oncology is associated with an increase in multiple immune-related adverse events (irAEs), whose optimal prevention and management remain unclear. In this context, there is a need for reliable and validated biomarkers to predict the occurrence of irAEs in patients treated with ICIs. Thus, the main objective of this study is to evaluate the diagnostic performance of a sensitive routinely available panel of autoantibodies consisting of antinuclear antibodies, rheumatoid factor, and antineutrophil cytoplasmic antibodies to identify patients at risk of developing irAEs. A multicenter, prospective, observational, cohort study has been designed to be conducted in patients diagnosed with cancer amenable to ICI therapy. Considering the percentage of ICI-induced irAEs to be 25% and a loss to follow-up of 5%, it has been estimated that a sample size of 294 patients is required to detect an expected sensitivity of the autoantibody panel under study of 0.90 with a confidence interval (95%) of no less than 0.75. For 48 weeks, patients will be monitored through the oncology outpatient clinics of five hospitals in Spain. Immune-related adverse events will be defined and categorized according to CTCAE v. 5.0. All the patients will undergo ordinary blood tests at specific moments predefined per protocol and extraordinary blood tests at the time of any irAE being detected. Ordinary and extraordinary samples will be frozen and stored in the biobank until analysis in the same autoimmunity laboratory when the whole cohort reaches week 48. A predictive model of irAEs will be constructed with potential risk factors of immune-related toxicity including the autoantibody panel under study. This protocol was reviewed and approved by the Ethical Committee of the Basque Country and the Spanish Agency of Medicines and Medical Devices. Informed consent will be obtained from all participants before their enrollment. The authors declare that the results will be submitted to an international peer-reviewed journal for their prompt dissemination.
Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, MO 64108, USA. Electronic address:
Antibody-based checkpoint inhibitors have achieved great success in cancer immunotherapy, but their uncontrollable immune-related adverse events remain a major challenge. In this study, we developed a tumor-activated nanoparticle that is specifically active in tumors but not in normal tissues. We discovered a short anti-PD-L1 peptide that blocks the PD-1/PD-L1 interaction.
Background: Immune checkpoint inhibitors (ICIs) have revolutionised oncology care, by enhancing the body's T cell lymphocyte response against tumour cells. ICIs block the inhibitory signalling between tumour cells and the immune system, but consequently reduce immunological tolerance. Subsequently for some, this leads to immune-related adverse events (irAE), a spectrum term for autoimmune-like toxicities induced by ICIs that affects various tissues and organs.
Background: Selective serotonin reuptake inhibitors (SSRIs) are the primary choice for antidepressant therapy in cancer patients with depression. Programmed death-1 and programmed cell death-ligand 1 (PD-1/PD-L1) play a critical role in immune checkpoint inhibitors. To date, there have been no studies reporting adverse events (AEs) associated with the real-world use of PD-1/PD-L1 inhibitors-SSRIs combination.
Objective: To describe presentation, treatment and outcome of immune checkpoint inhibitor (ICI) associated-vasculitis in cancer patients in a multicentre study.
Methods: Thanks to the ImmunoCancer International Registry (ICIR), a multidisciplinary network focused on the research of the immune related adverse events related to cancer immunotherapies, patients presenting with a clinical and/or radiological suspicion of vasculitis, and histological evidence of vasculitis after being exposed to ICIs were retrospectively identified.
Results: Twenty eight cases were identified in the ICIR registry.
