{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T10:57:35Z","timestamp":1784977055222,"version":"3.55.0"},"reference-count":110,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T00:00:00Z","timestamp":1706054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Partner Therapeutics, Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Immune checkpoint inhibitor (ICI) therapy improves outcomes in several cancers. Unfortunately, many patients experience grade 3\u20134 treatment-related adverse events, including gastrointestinal (GI) toxicities which are common. These GI immune-related adverse events (irAEs) induced by ICIs present significant clinical challenges, require prompt intervention, and result in treatment delays or discontinuations. The treatment for these potentially severe and even fatal GI irAEs which include enterocolitis, severe diarrhea, and hepatitis may interfere with the anti-cancer approach. Sargramostim (glycosylated, yeast-derived, recombinant human GM-CSF) is an agent that has been used in clinical practice for more than 30 years with a well-recognized safety profile and has been studied in many therapeutic areas. The mechanism of action of sargramostim may treat moderate-to-severe GI irAEs without impairing the anti-cancer therapy. Some early data also suggest a potential survival benefit. Through the differentiation\/maturation of monocytes, macrophages, and neutrophils and induction of anti-inflammatory T cell responses, GM-CSF aids in GI homeostasis, mucosal healing, and mucosal immunity. GM-CSF knockout mice are susceptible to severe colitis which was prevented with murine GM-CSF administration. For some patients with GI mucosa and immune cell function impairment, e.g., Crohn\u2019s disease, sargramostim reduces disease severity. In a prospective, randomized study (ECOG 1608), advanced melanoma patients had a reduction in grade 3\u20135 GI irAEs and less frequent colonic perforation in the sargramostim plus ipilimumab arm compared to ipilimumab alone. Sargramostim continues to be studied with ICIs for the prophylactic management of irAEs while also potentially providing a survival benefit.<\/jats:p>","DOI":"10.3390\/cancers16030501","type":"journal-article","created":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T07:42:16Z","timestamp":1706082136000},"page":"501","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Sargramostim for Prophylactic Management of Gastrointestinal Immune-Related Adverse Events of Immune Checkpoint Inhibitor Therapy for Cancer"],"prefix":"10.3390","volume":"16","author":[{"given":"Michael","family":"Dougan","sequence":"first","affiliation":[{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA"},{"name":"Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA"},{"name":"Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Buchbinder","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA"},{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1159-5607","authenticated-orcid":false,"given":"Hillard","family":"Lazarus","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology and Oncology, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4828","DOI":"10.1200\/JCO.2011.38.0899","article-title":"Cancer immunotherapy comes of age","volume":"29","author":"Topalian","year":"2011","journal-title":"J. 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