Sargramostim is primarily used for myeloid reconstitution after autologous or allogeneic bone marrow transplantation. It is also used to treat neutropenia induced by chemotherapy during the treatment of acute myeloid leukemia. Additionally, it is used as a medical countermeasure for treating people who have been exposed to sufficient radiation to suppress bone marrow myelogenesis.[1]
It is administered via intravenous infusion or via subcutaneous injection.[1]
Contraindications
Sargramostim should not be used in people with known hypersensitivity to GM-CSF, yeast-derived products or any component of the product and for concomitant use with chemotherapy and radiotherapy.[1]
There is a formulation with benzyl alcohol, which is toxic to babies; other formulations should be used. Sargramostim has not been tested in pregnant women but appears to be toxic to fetuses. There is no data as to whether sargramostim is expressed in breast milk.[1]
Sargramostim is a version of GM-CSF, which has a normal role in human biology, causing progenitor cells to differentiate into neutrophils, monocytes, macrophages, and, myeloid-derived dendritic cells; it can also activate mature granulocytes and macrophages, and can contribute to the differentiation of megakaryocytic progenitors and erythroid progenitor cells.[1]
Chemistry
Sargramostim is a recombinant version of GM-CSF, which is a glycoprotein made of 127 amino acids; sargramostim is mixture of three versions of GM-CSF that have molecular weights of 19,500, 16,800 and 15,500 daltons. It is manufactured in yeast.[1]
History
The sequence of human GM-CSF was first identified in 1985 and soon three recominbant human GM-CSFs were produced, one in bacteria, one in mammalian cells, and one in yeast;[2]Immunex developed GM-CSF manufactured in yeast into Leukine.[3] Clinical trials of sargramostim were initiated in 1987;[4] in that same year it was administered to six people as part of a compassionate-use protocol for the victims of cesium irradiation from the Goiânia accident.[5]
In January 2008, Bayer informed healthcare professionals of the market withdrawal of the current liquid formulation of sargramostim. The liquid formulation was withdrawn because of an upward trend in spontaneous reports of adverse reactions, including syncope (fainting), which are temporally correlated with a change that was made to the formulation around April 2007 to include edetate disodium (EDTA).[3] The upward trend in adverse reaction reporting rates had not been observed with the use of lyophilized sargramostim.[8] The original liquid formulation without EDTA was returned to the market in the US in May 2008.[9]
In 2009, Genzyme acquired the rights to Leukine from Bayer, including the manufacturing facility in the Seattle area.[4][10][11]
In March 2018 the label was extended to use as a countermeasure for acute radiation syndrome.[12]
On February 1, 2018, Partner Therapeutics, Inc. acquired the global rights to develop, manufacture, and commercialize Leukine (sargramostim) from Sanofi.[13]
^"Approval Summary for sargramostim". Oncology Tools. U.S. Food and Drug Administration, Center for Drug Evaluation and Research. 1991-03-05. Archived from the original on 2007-06-24. Retrieved 20 September 2009.
