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      Sneaky side effects and ineffectiveness of an immunotherapy with ipilimumab in a case of metastatic melanoma

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          ABSTRACT

          Ipilimumab is an anti-CTLA-4 antibody that is approved for the treatment of metastatic malignant melanoma. Side-effects are mostly immune-mediated and in many cases the lack of specific symptoms leads to delayed diagnosis and treatment of adverse events. We present the case of a female patient who experienced an uncommon combination of adverse reactions while undergoing therapy with ipilimumab and where the absence of specificity of the symptoms led to late diagnosis and treatment of side effects. Autoimmune disease was neither associated with tumor response nor with prolonged survival.

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          Radiologic manifestations of immune-related adverse events in patients with metastatic melanoma undergoing anti-CTLA-4 antibody therapy.

          Yulia Bronstein, S Ng, Wen-Jen Hwu … (2011)
          Monoclonal antibodies against cytotoxic T-lymphocyte antigen 4 (CTLA-4) used for treatment of metastatic melanoma produce inflammatory immune-related adverse events. The purpose of the current study was to retrospectively identify and characterize the radiologic manifestations of immune-related adverse events and to evaluate the possible association between these events and clinical responses to anti-CTLA-4 therapy. We retrospectively reviewed the images and medical records of 119 patients with metastatic melanoma treated with anti-CTLA-4 at our institution and assessed the presence of radiologic manifestations of immune-related adverse events and the clinical responses to therapy. The responses were categorized as progressive or controlled disease. The controlled disease category included stable disease, partial response, and complete response according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Radiologic manifestations of immune-related adverse events were found in 20 patients (16.8%). Clinically evident manifestations included colitis, hypophysitis, thyroiditis, and arthritis. Clinically silent manifestations were benign lymphadenopathy and inflammatory changes in the soft tissues, such as myositis, fasciitis, and retroperitoneal fat haziness. There was a significant association between the incidence of radiologic manifestations of immune-related adverse events and clinical responses to anti-CTLA-4 therapy. The disease control rates were 18% for the entire group, 55% for the group with, and 10% for the group without radiologic manifestations of immune-related adverse events. In three patients (2.5%), lymphadenopathy related to radiologic manifestations of immune-related adverse events was interpreted as suspected metastasis but was proved benign at biopsy. Radiologic manifestations of immune-related adverse events are associated with significant clinical benefit of anti-CTLA-4 therapy. In the era of developing immune checkpoint-targeted therapy for metastatic melanoma, radiologists should be alert to the possibility of these manifestations, which can mimic radiologic disease progression.
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            Efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy

            S Bowyer, P Prithviraj, P Lorigan … (2016)
            Background: Recent phase III clinical trials have established the superiority of the anti-PD-1 antibodies pembrolizumab and nivolumab over the anti-CTLA-4 antibody ipilimumab in the first-line treatment of patients with advanced melanoma. Ipilimumab will be considered for second-line treatment after the failure of anti-PD-1 therapy. Methods: We retrospectively identified a cohort of 40 patients with metastatic melanoma who received single-agent anti-PD-1 therapy with pembrolizumab or nivolumab and were treated on progression with ipilimumab at a dose of 3 mg kg−1 for a maximum of four doses. Results: Ten percent of patients achieved an objective response to ipilimumab, and an additional 8% experienced prolonged (>6 months) stable disease. Thirty-five percent of patients developed grade 3–5 immune-related toxicity associated with ipilimumab therapy. The most common high-grade immune-related toxicity was diarrhoea. Three patients (7%) developed grade 3–5 pneumonitis leading to death in one patient. Conclusions: Ipilimumab therapy can induce responses in patients who fail the anti-PD-1 therapy with response rates comparable to previous reports. There appears to be an increased frequency of high-grade immune-related adverse events including pneumonitis that warrants close surveillance.
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              Drug-associated dermatomyositis following ipilimumab therapy: a novel immune-mediated adverse event associated with cytotoxic T-lymphocyte antigen 4 blockade.

              Shirwa Sheik Ali, Allison Goddard, Jason J. Luke … (2015)
              Ipilimumab, a human monoclonal antibody targeted against cytotoxic T-lymphocyte antigen 4, has shown promise in the treatment of metastatic melanoma. However, given its mechanism of action, immune-related adverse effects have been reported with this therapy. Despite increasing reports of immune-related adverse effects related to ipilimumab therapy, dermatomyositis associated with this agent has not previously been reported.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Dermatoendocrinol
                Journal ID (iso-abbrev): Dermatoendocrinol
                Journal ID (publisher-id): KDER
                Journal ID (publisher-id): kder20
                Title: Dermato-endocrinology
                Publisher: Taylor & Francis
                ISSN (Print): 1938-1972
                ISSN (Electronic): 1938-1980
                Publication date Collection: Jan-Dec 2016
                Publication date (Electronic): 30 June 2016
                Publication date PMC-release: 30 June 2016
                Volume: 8
                Issue: 1
                Electronic Location Identifier: e1199307
                Affiliations
                [a ]Department of Dermatology, Saarland University Medical School , Homburg/Saar, Germany
                [b ]Department for Diagnostic and Interventional Neuroradiology, Saarland University Medical School , Homburg/Saar, Germany
                [c ]Department of Internal Medicine II, Saarland University Medical School , Homburg/Saar, Germany
                Author notes
                CONTACT Prof. Dr. Claudia Pföhler: claudia.pfoehler@ 123456uks.eu , Saarland University Medical School, Department of Dermatology , 66421 Homburg/Saar, Germany
                Article
                Publisher ID: 1199307
                DOI: 10.1080/19381980.2016.1199307
                PMC ID: 4977105
                SO-VID: f0808abf-91ee-4505-b035-fbe8155c372c
                Copyright © © 2016 The Author(s). Published with license by Taylor & Francis.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.

                History
                Date received : 24 May 2016
                Date accepted : 3 June 2016
                Page count
                Figures: 1, Tables: 1, References: 20, Pages: 4
                Categories
                Subject: Research Paper

                ScienceOpen disciplines: Dermatology
                Keywords: autoimmunity,ipilimumab,immunology,melanoma,orbital myositis,side effects,vitiligo
                Data availability:
                ScienceOpen disciplines: Dermatology
                Keywords: autoimmunity, ipilimumab, immunology, melanoma, orbital myositis, side effects, vitiligo

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