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Case Report

Multiple high-grade and rare immune-related adverse events in a colon cancer patient with genomic and cytokine profiling

    Kevin Tyan‡

    Harvard Medical School, Boston, MA 02115, USA

    ‡These two authors contributed equally to the manuscript

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    ,
    Osama Abu-Shawer‡

    Harvard Medical School, Boston, MA 02115, USA

    Cleveland Clinic, Cleveland, OH 44195, USA

    ‡These two authors contributed equally to the manuscript

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    ,
    Joanna Baginska

    Department of Medical Oncology, Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA

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    ,
    Mariano Severgnini

    Department of Medical Oncology, Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA

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    ,
    Michael Manos

    Department of Medical Oncology, Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA

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    ,
    Henrikas Vaitkevicius

    Department of Neurology, Brigham & Women's Hospital, Boston, MA 02115, USA

    Marinus Pharmaceuticals, Radnor, PA 19087, USA

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    ,
    Shilpa Grover

    Harvard Medical School, Boston, MA 02115, USA

    Division of Gastroenterology, Department of Medicine, Brigham & Women's Hospital, Boston, MA 02115, USA

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    ,
    F Stephen Hodi

    Harvard Medical School, Boston, MA 02115, USA

    Department of Medical Oncology, Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA

    Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA

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    &
    Osama E Rahma

    *Author for correspondence: Tel.: +1 617 632 6954;

    E-mail Address: Osamae_rahma@DFCI.harvard.edu

    Harvard Medical School, Boston, MA 02115, USA

    Department of Medical Oncology, Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA

    Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA

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    Published Online:13 Jun 2022https://doi.org/10.2217/imt-2021-0298

    Abstract

    We report a case of multiple high-grade and rare immune-related adverse events (irAEs) in a patient with microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). A middle-aged MSI-H mCRC patient with metastases to the lungs and lymph nodes received several lines of chemotherapy and immunotherapy and developed five different high-grade irAEs during immunotherapy, including lymphadenitis, pneumonitis, hypophysitis, thyroiditis and transverse myelitis. Genomic profiling revealed high tumor mutational burden of 43 Muts/Mb. Cytokine profiling showed a threefold increase in MMP-9 shortly prior to the onset of lymphadenitis and a fourfold increase of Ang-1 1 week after the resolution of lymphadenitis. Further studies are warranted to investigate the association of MSI-H mCRC with irAEs and the role of cytokines in predicting irAEs.

    Plain language summary

    Immune-related adverse events (irAEs) are a potential side effect of taking immunotherapy treatment for cancer. We report a case of a patient with a highly mutated form of metastatic colon cancer who developed five unique and severe irAEs while receiving immunotherapy. The patient developed inflammation of the lymph nodes, lungs, pituitary gland, thyroid and spinal cord. Genetic testing showed that the tumor was highly mutated (43 Muts/Mb). Analysis of cell signaling proteins called cytokines revealed that MMP-9 sharply increased before the onset of lymphadenitis and Ang-1 sharply increased after its resolution. Further research is needed to understand the relationship between highly mutated colon cancer and irAEs as well as the role of cytokines in predicting the onset and resolution of irAEs.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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