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      Arthritis and Myositis in a Patient Treated with Programmed Cell Death-1 (PD-1) Inhibitor Pembrolizumab for Lung Cancer

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          Abstract

          Immune checkpoint inhibitors (ICIs) are a new class of drug that have demonstrated efficacy across many cancer types. Because of their nature and mode of action, ICIs unleash immune activation raising concerns as to whether they can be used in patients with concomitant autoimmune or auto-inflammatory diseases. Their usage can lead to the development of autoimmune phenomena known as immune related adverse events (irAEs), virtually affecting every organ. As the use of ICIs is drastically increasing, evidence of irAEs has been accumulating. Herein, we report a case of inflammatory myositis and arthritis 6 months after pembrolizumab therapy, an anti-programmed death-1 (PD1) ICI in a patient with lung cancer, aiming at raising awareness of the diagnostic and clinical challenges clinicians may face when checkpoint inhibitors-related rheumatologic irAEs are developed.

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          The blockade of immune checkpoints in cancer immunotherapy.

          Drew M Pardoll (2012)
          Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
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            Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline

            Julie Brahmer, Christina Lacchetti, Bryan J Schneider … (2018)
            Purpose To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events in patients treated with immune checkpoint inhibitor (ICPi) therapy. Methods A multidisciplinary, multi-organizational panel of experts in medical oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, urology, neurology, hematology, emergency medicine, nursing, trialist, and advocacy was convened to develop the clinical practice guideline. Guideline development involved a systematic review of the literature and an informal consensus process. The systematic review focused on guidelines, systematic reviews and meta-analyses, randomized controlled trials, and case series published from 2000 through 2017. Results The systematic review identified 204 eligible publications. Much of the evidence consisted of systematic reviews of observational data, consensus guidelines, case series, and case reports. Due to the paucity of high-quality evidence on management of immune-related adverse events, recommendations are based on expert consensus. Recommendations Recommendations for specific organ system-based toxicity diagnosis and management are presented. While management varies according to organ system affected, in general, ICPi therapy should be continued with close monitoring for grade 1 toxicities, with the exception of some neurologic, hematologic, and cardiac toxicities. ICPi therapy may be suspended for most grade 2 toxicities, with consideration of resuming when symptoms revert to grade 1 or less. Corticosteroids may be administered. Grade 3 toxicities generally warrant suspension of ICPis and the initiation of high-dose corticosteroids (prednisone 1 to 2 mg/kg/d or methylprednisolone 1 to 2 mg/kg/d). Corticosteroids should be tapered over the course of at least 4 to 6 weeks. Some refractory cases may require infliximab or other immunosuppressive therapy. In general, permanent discontinuation of ICPis is recommended with grade 4 toxicities, with the exception of endocrinopathies that have been controlled by hormone replacement. Additional information is available at www.asco.org/supportive-care-guidelines and www.asco.org/guidelineswiki .
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              PD-1 and PD-1 ligands: from discovery to clinical application.

              Taku Okazaki, Tasuku HONJO (2007)
              Programmed cell death-1 (PD-1, Pdcd1), an immunoreceptor belonging to the CD28/CTLA-4 family negatively regulates antigen receptor signaling by recruiting protein tyrosine phosphatase, SHP-2 upon interacting with either of two ligands, PD-L1 or PD-L2. Because of the wide range of ligand distribution in the body, its biological significance pervades almost every aspect of immune responses including autoimmunity, tumor immunity, infectious immunity, transplantation immunity, allergy and immunological privilege. In this review, we would like to summarize the history of PD-1 research since its discovery and recent findings that suggest promising future for the clinical application of PD-1 agonists and antagonists to various human diseases.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Mediterr J Rheumatol
                Journal ID (iso-abbrev): Mediterr J Rheumatol
                Journal ID (publisher-id): MJR
                Title: Mediterranean Journal of Rheumatology
                Publisher: The Mediterranean Journal of Rheumatology (MJR)
                ISSN (Electronic): 2529-198X
                Publication date Collection: September 2020
                Publication date (Electronic): 30 September 2020
                Volume: 31
                Issue: 3
                Pages: 355-357
                Affiliations
                [1 ]Department of Rheumatology and Clinical Immunology and
                [2 ]Department of Oncology, University General Hospital of Larissa, School of Health Sciences University of Thessaly, Larissa, Greece
                Author notes
                Corresponding Author: Theodora Simopoulou, MD, PhD, Department of Rheumatology, and Clinical Immunology, University General Hospital of Larissa, School of Health Sciences, University of Thessaly, Mezourlo 41110 Larissa, Thessaly, Greece, Tel.: +30 2413 502 879, Fax: +302413501016, E-mail: thsimopoul@ 123456med.uth.gr
                Author information
                https://orcid.org/0000-0002-5755-1538
                https://orcid.org/0000-0003-2604-5090
                https://orcid.org/0000-0002-5530-6774
                https://orcid.org/0000-0002-9697-7902
                Article
                Publisher ID: MJR-31-3-355
                DOI: 10.31138/mjr.31.3.355
                PMC ID: 7641028
                PubMed ID: 33163870
                SO-VID: 7ff45aed-7dfd-4337-a0fc-55a12f148d5d
                Copyright © © 2020 The Mediterranean Journal of Rheumatology (MJR)
                License:

                This work is licensed under and Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                Date received : 17 March 2020
                Date revision received : 17 June 2020
                Date accepted : 30 June 2020
                Categories
                Subject: Article

                Keywords: immune checkpoint inhibitors,immune related adverse events,myositis,arthritis
                Data availability:
                Keywords: immune checkpoint inhibitors, immune related adverse events, myositis, arthritis

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