Sargramostim and immune checkpoint inhibitors: combinatorial therapeutic studies in metastatic melanoma

Immunotherapy. 2021 Aug;13(12):1011-1029. doi: 10.2217/imt-2021-0119. Epub 2021 Jun 23.


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, a yeast-derived recombinant human GM-CSF, has shown clinical activity against diverse solid tumors, including metastatic melanoma. Here we review the 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.

Keywords: GM-CSF; adaptive immunity; immune checkpoint inhibitors; immune-related adverse event; innate immunity; ipilimumab; melanoma; nivolumab; pembrolizumab; sargramostim.

Plain language summary

Lay abstract 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 (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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Drug Synergism
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage*
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage*
  • Melanoma / drug therapy*
  • Recombinant Proteins / administration & dosage


  • Immune Checkpoint Inhibitors
  • Recombinant Proteins
  • sargramostim
  • Granulocyte-Macrophage Colony-Stimulating Factor