This review, which has been recently published in our partner journal Immunotherapy, summarizes the potential of sargramostim to augment the immune response and increase antitumor efficacy in patients with metastatic melanoma, while modulating immune-related toxicity. The authors further discuss the additional immunomodulatory potential of sargramostim. Results from a randomized Phase II trial showed sargramostim plus ipilimumab improved overall survival compared with ipilimumab monotherapy and reduced ipilimumab-related toxicities. These findings were also supported by two real-world trials evaluating sargramostim in combination with ipilimumab. Results of ongoing studies evaluating sargramostim in combination with ipilimumab, ipilimumab/nivolumab, and other immunotherapeutics are awaited.
The use of immune checkpoint inhibitors in patients with metastatic melanoma generates clinical benefit, including improved survival. Yet disease resistance and immune-related adverse events persist as unmet needs. Sargramostim, yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF), has shown clinical activity against diverse solid tumors, including metastatic melanoma. Here, we review use of sargramostim for treatment of advanced melanoma. Potential sargramostim applications in melanoma draw on the unique ability of GM-CSF to link innate and adaptive immune responses. We review preclinical and translational data describing the mechanism of action of sargramostim and synergy with immune checkpoint inhibitors to enhance efficacy and reduce treatment-related toxicity.
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Immune checkpoint inhibitors are medications that help the immune system to fight cancer. Side effects with these medicines may occur because the immune system may attack healthy cells. Sargramostim is a medication that is similar to a protein in the body (granulocyte-macrophage colony-stimulating factor [GM-CSF]). Studies have shown that sargramostim can fight cancer, including melanoma. When sargramostim is used with immune checkpoint inhibitors, the body’s natural defense to fight cancer (the immune system) is boosted and some side effects are reduced. This article reviews how GM-CSF is thought to boost the immune system’s response against cancer in the laboratory and in animal models. We also review the use of sargramostim alone and combined with ipilimumab in patients with advanced melanoma.