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      Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group


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          Cancer immunotherapy has transformed the treatment of cancer. However, increasing use of immune-based therapies, including the widely used class of agents known as immune checkpoint inhibitors, has exposed a discrete group of immune-related adverse events (irAEs). Many of these are driven by the same immunologic mechanisms responsible for the drugs’ therapeutic effects, namely blockade of inhibitory mechanisms that suppress the immune system and protect body tissues from an unconstrained acute or chronic immune response. Skin, gut, endocrine, lung and musculoskeletal irAEs are relatively common, whereas cardiovascular, hematologic, renal, neurologic and ophthalmologic irAEs occur much less frequently. The majority of irAEs are mild to moderate in severity; however, serious and occasionally life-threatening irAEs are reported in the literature, and treatment-related deaths occur in up to 2% of patients, varying by ICI. Immunotherapy-related irAEs typically have a delayed onset and prolonged duration compared to adverse events from chemotherapy, and effective management depends on early recognition and prompt intervention with immune suppression and/or immunomodulatory strategies. There is an urgent need for multidisciplinary guidance reflecting broad-based perspectives on how to recognize, report and manage organ-specific toxicities until evidence-based data are available to inform clinical decision-making. The Society for Immunotherapy of Cancer (SITC) established a multidisciplinary Toxicity Management Working Group, which met for a full-day workshop to develop recommendations to standardize management of irAEs. Here we present their consensus recommendations on managing toxicities associated with immune checkpoint inhibitor therapy.

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          The online version of this article (10.1186/s40425-017-0300-z) contains supplementary material, which is available to authorized users.

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          Incidence of Programmed Cell Death 1 Inhibitor-Related Pneumonitis in Patients With Advanced Cancer: A Systematic Review and Meta-analysis.

          Programmed cell death 1 (PD-1) inhibitor-related pneumonitis is a rare but clinically serious and potentially life-threatening adverse event. Little is known about its incidence across different tumor types and treatment regimens.
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              Development of immuno-oncology drugs - from CTLA4 to PD1 to the next generations.

              Axel Hoos (2016)
              Since the regulatory approval of ipilimumab in 2011, the field of cancer immunotherapy has been experiencing a renaissance. This success is based on progress in both preclinical and clinical science, including the development of new methods of investigation. Immuno-oncology has become a sub-specialty within oncology owing to its unique science and its potential for substantial and long-term clinical benefit. Immunotherapy agents do not directly attack the tumour but instead mobilize the immune system - this can be achieved through various approaches that utilize adaptive or innate immunity. Therefore, immuno-oncology drug development encompasses a broad range of agents, including antibodies, peptides, proteins, small molecules, adjuvants, cytokines, oncolytic viruses, bi-specific molecules and cellular therapies. This Perspective summarizes the recent history of cancer immunotherapy, including the factors that led to its success, provides an overview of novel drug-development considerations, summarizes three generations of immunotherapies that have been developed since 2011 and, thus, illustrates the breadth of opportunities these new generations of immunotherapies represent.

                Author and article information

                J Immunother Cancer
                J Immunother Cancer
                Journal for Immunotherapy of Cancer
                BioMed Central (London )
                21 November 2017
                21 November 2017
                : 5
                : 95
                [1 ]Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263 USA
                [2 ]ISNI 0000 0001 2291 4776, GRID grid.240145.6, University of Texas MD Anderson Cancer Center, ; Houston, TX USA
                [3 ]ISNI 0000 0001 2260 0793, GRID grid.417993.1, Merck & Co., Inc., ; Upper Gwynedd, PA USA
                [4 ]ISNI 0000 0001 2171 9311, GRID grid.21107.35, Johns Hopkins University, ; Baltimore, MD USA
                [5 ]GRID grid.419971.3, Bristol-Myers Squibb Company, ; New York, NY USA
                [6 ]ISNI 0000 0001 2171 9952, GRID grid.51462.34, Memorial Sloan Kettering Cancer Center, ; New York, NY USA
                [7 ]ISNI 0000 0004 0460 3896, GRID grid.417747.6, Dana Farber/Brigham and Women’s Cancer Center, ; Boston, MA USA
                [8 ]ISNI 0000 0001 2355 7002, GRID grid.4367.6, Washington University in St Louis, ; St Louis, MO USA
                [9 ]ISNI 0000 0001 0790 959X, GRID grid.411377.7, Indiana University, ; Indianapolis, IN USA
                [10 ]ISNI 0000 0004 1936 7822, GRID grid.170205.1, University of Chicago, ; Chicago, IL USA
                [11 ]ISNI 0000 0001 1017 3800, GRID grid.423114.1, Oncology Nursing Society, ; Pittsburgh, PA USA
                [12 ]ISNI 0000 0004 0386 9924, GRID grid.32224.35, Massachusetts General Hospital, ; Boston, MA USA
                © The Author(s). 2017

                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.

                : 26 September 2017
                : 6 November 2017
                Position Article and Guidelines
                Custom metadata
                © The Author(s) 2017

                immune-related adverse events,toxicity,immune checkpoint inhibitor


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