부산대학교 도서관

Simple Summary: Recently, cancer prognoses have improved by using a new class of drugs called immune checkpoint inhibitors. These treatments work by helping a person's immune system better recognize and kill cancer cells. Unfortunately, these drugs may cause the immune system to attack normal (i.e., non-cancerous) tissues and can cause serious organ injury. One common and severe toxicity is colitis—inflammation of the bowels—leading to diarrhea, bleeding, and, rarely, death. Sargramostim (recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF)) has been used clinically for nearly 30 years and has been used as a treatment adjunct for other inflammatory diseases of the bowel, such as Crohn's disease or ulcerative colitis. Some data suggest that it may be an effective treatment in preventing the side effects of immune checkpoint inhibitor therapy by speeding up the maturation of different blood cells and may quiet inflammation and improve healing in the gastrointestinal tract. Sargramostim may even be linked to prolonged patient survival. Immune checkpoint inhibitor (ICI) therapy improves outcomes in several cancers. Unfortunately, many patients experience grade 3–4 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's disease, sargramostim reduces disease severity. In a prospective, randomized study (ECOG 1608), advanced melanoma patients had a reduction in grade 3–5 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. [ABSTRACT FROM AUTHOR]