Sargramostim

Summary

Sargramostim is a recombinant yeast-derived GM-CSF used to accelerate myeloid recovery following chemotherapy, bone marrow transplantation, and hematopoietic stem cell transplantation. It also has indications for mobilization of hematopoietic progenitor cells and treatment of graft failure. Additionally, it is approved for radiation-induced myelosuppression (acute radiation syndrome).

Mechanism of Action

Binds to GM-CSF receptors on hematopoietic progenitor cells, stimulating proliferation, differentiation, and activation of granulocytes, macrophages, and dendritic cells; enhances neutrophil and monocyte function and accelerates myeloid recovery.

Routes of Administration

Goals & Uses

• Treatment of acute radiation syndrome (ARS)Radiation Emergency CountermeasureModerate
• Neutrophil recovery in AML induction chemotherapyOncology Supportive CareHigh
• Graft failure or engraftment delayHematopoietic SupportModerate
• Mobilization of hematopoietic progenitor cellsHematologyHigh
• Accelerate myeloid recovery after bone marrow transplantationHematopoietic SupportHigh
• Immunomodulation in COVID-19 (investigational)ImmunotherapyLow

Contraindications

• Hypersensitivity to sargramostim, yeast-derived products, or any componentAllergyHigh
• Neonates (benzyl alcohol-containing formulation)PediatricHigh
• Concurrent use with chemotherapy or radiotherapyOncologyHigh
• Excessive leukemic myeloid blasts in bone marrow or peripheral blood (≥10%)OncologyHigh

Adverse Effects

• Bone painMusculoskeletalCommon
• Fever and constitutional symptomsGeneralCommon
• Fluid retention / peripheral edemaCardiovascularUncommon
• Injection site reactionsLocalCommon
• Capillary leak syndromeVascularRareLeakage of fluid from blood vessels into tissues
• First-dose reaction (flushing, hypotension, tachycardia, dyspnea)HypersensitivityUncommon

Drug Interactions

• Cytotoxic chemotherapy agentsHigh
• WarfarinModerate
• CorticosteroidsLow
• LithiumLow

Population Constraints

• PregnancyReproductive SafetyRelative
• Neonates / premature infants (benzyl alcohol formulation)PediatricAbsolute
• Patients with pre-existing pulmonary diseaseRespiratoryRelative
• Patients with pre-existing cardiac diseaseCardiovascularRelative
• Renal or hepatic impairmentOrgan DysfunctionRelative

Regulatory Status

• European UnionUnapprovedSargramostim is not approved in the EU; molgramostim (E. coli-derived GM-CSF) has been used historically but is also not currently authorized.
• United StatesApprovedApproved: Myeloid reconstitution after autologous BMT, Myeloid reconstitution after allogeneic BMT, Induction chemotherapy in acute myelogenous leukemia (AML) in patients ≥55 years, Peripheral blood progenitor cell mobilization and post-transplant myeloid reconstitution, BMT graft failure or engraftment delay, Hematopoietic subsyndrome of acute radiation syndrome (H-ARS)Approved by FDA; marketed as Leukine (sargramostim) by Partner Therapeutics.
• United KingdomUnapprovedNot approved by MHRA as of current knowledge cutoff; G-CSF products (filgrastim, lenograstim) are preferred in the UK.

FDA-approved under BLA. Approved indications include myeloid reconstitution after autologous/allogeneic BMT, induction chemotherapy in AML, peripheral blood progenitor cell mobilization and post-transplant engraftment, and acute exposure to myelosuppressive doses of radiation. Orphan Drug designation for certain indications.

Evidence & Sources

No sources recorded yet.