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      Complete response of metastatic melanoma in a patient with Crohn’s disease simultaneously receiving anti-α4β7 and anti-PD1 antibodies

      case-report

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          Abstract

          Background

          Immune checkpoint inhibitors (ICPIs) are increasingly being used in the treatment of a variety of malignancies. The original studies that demonstrated the efficacy of ICPIs excluded patients actively being treated for autoimmune conditions, and there is only limited evidence that these treatments are safe and effective in this population of patients.

          Case presentation

          We present a case of a man with Crohn’s disease actively requiring immunosuppressive therapy who subsequently received pembrolizumab for metastatic melanoma. He had no further progression of metastatic disease and had resolution of his pulmonary nodule while he experienced no Crohn’s disease flares or immune related adverse events. We surveyed the existing literature for studies examining the use of ICPIs in patients with autoimmune disorders and reviewed the unique mechanism of action of the α4β7 inhibitor, vedolizumab.

          Conclusion

          Patients with autoimmune conditions should be considered candidates for immune checkpoint inhibition even in the setting of active immunosuppressive therapy. The mechanism of action of immunosuppressive therapy should be considered with the most targeted form of treatment being used when possible. Further prospective studies investigating immunotherapy in patients with autoimmune conditions are warranted.

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          Most cited references6

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          Use of Immune Checkpoint Inhibitors in the Treatment of Patients With Cancer and Preexisting Autoimmune Disease

          Cancer immunotherapy with checkpoint inhibitors (CPIs) is associated with frequent immune-related adverse events (irAEs) and is often not recommended for patients with concomitant autoimmune disease.
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            A randomized, double-blind, placebo-controlled, phase II study comparing the tolerability and efficacy of ipilimumab administered with or without prophylactic budesonide in patients with unresectable stage III or IV melanoma.

            Diarrhea (with or without colitis) is an immune-related adverse event (irAE) associated with ipilimumab. A randomized, double-blind, placebo-controlled, multicenter, multinational phase II trial was conducted to determine whether prophylactic budesonide (Entocort EC), a nonabsorbed oral steroid, reduced the rate of grade >or=2 diarrhea in ipilimumab-treated patients with advanced melanoma. Previously treated and treatment-naïve patients (N = 115) with unresectable stage III or IV melanoma received open-label ipilimumab (10 mg/kg every 3 weeks for four doses) with daily blinded budesonide (group A) or placebo (group B) through week 16. The first scheduled tumor evaluation was at week 12; eligible patients received maintenance treatment starting at week 24. Diarrhea was assessed using Common Terminology Criteria for Adverse Events (CTCAE) 3.0. Patients kept a diary describing their bowel habits. Budesonide did not affect the rate of grade >or=2 diarrhea, which occurred in 32.7% and 35.0% of patients in groups A and B, respectively. There were no bowel perforations or treatment-related deaths. Best overall response rates were 12.1% in group A and 15.8% in group B, with a median overall survival of 17.7 and 19.3 months, respectively. Within each group, the disease control rate was higher in patients with grade 3 to 4 irAEs than in patients with grade 0 to 2 irAEs, although many patients with grade 1 to 2 irAEs experienced clinical benefit. Novel patterns of response to ipilimumab were observed. Ipilimumab shows activity in advanced melanoma, with encouraging survival and manageable adverse events. Budesonide should not be used prophylactically for grade >or=2 diarrhea associated with ipilimumab therapy.
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              Integrin signalling and function in immune cells.

              Integrins not only mediate cell-cell and cell-extracellular matrix adhesion, but also affect the multitude of signal transduction cascades in control of cell survival, proliferation, differentiation and organ development. Mutations in integrins or the major effectors of integrin signalling pathways cause defective organ development, immunodeficiency, cancer or autoimmune disease. Understanding of the signalling events that drive integrin activation and signalling is therefore crucial to uncover the molecular mechanisms of these diseases. This review discusses the key signalling complexes regulating integrin activation and function in both 'inside-out' and 'outside-in' pathways in T lymphocytes, including kinases, SLP-76, VAV1, ADAP, SKAP-55, RapL, RIAM, Rap1, Talin and Kindlin. © 2012 Shanghai Institute of Biochemistry and Cell Biology, SIBS, CAS. Immunology © 2012 Blackwell Publishing Ltd.
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                Author and article information

                Contributors
                (773) 834-7961 , jluke@medicine.bsd.uchicago.edu
                Journal
                J Immunother Cancer
                J Immunother Cancer
                Journal for Immunotherapy of Cancer
                BioMed Central (London )
                2051-1426
                6 January 2019
                6 January 2019
                2019
                : 7
                : 1
                Affiliations
                [1 ]ISNI 0000 0004 1936 7822, GRID grid.170205.1, Department of Medicine, , University of Chicago, ; 5841 S. Maryland Ave. MC2115, Chicago, IL 60637 USA
                [2 ]Department of Medicine, Section of Gastroenterology, Inflammatory Bowel Disease Center, University of Chicago, Chicago, IL USA
                Article
                484
                10.1186/s40425-018-0484-x
                6322234
                30612589
                5e086c23-d04a-4e55-8f66-9993836045d0
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 4 August 2018
                : 13 December 2018
                Funding
                Funded by: Department of Defense Career Development Award
                Award ID: W81XWH-17-1-0265
                Award Recipient :
                Categories
                Case Report
                Custom metadata
                © The Author(s) 2019

                immune checkpoint inhibitor therapy,metastatic melanoma,crohn’s disease,autoimmune disease,immune related adverse event

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