Mechanism of Actionneptuneweb2021-04-19T06:53:20-04:00

LEUKINE® (sargramostim) activates multilineage immune defense against infection¹

LEUKINE is the first and only FDA-approved GM-CSF that supports the survival, growth, and activation of neutrophils, monocytes/macrophages, and myeloid-derived dendritic cells¹

Explore the hematopoietic cascade by clicking on the cell types below:

Multipotent hematopoietic stem cell^2-5*

Multipotent hematopoietic cascade diagram

Macrophage Neutrophil Dendritic Cell

Macrophage Neutrophil Dendritic Cell

*This image is a partial representation of the hematopoietic cascade. It does not include all cytokines necessary for hematopoiesis.

Neutrophil

neutrophil

Neutrophil: first responder

Neutrophils are the first line of immune defense against invading pathogens, including bacteria, fungi, and protozoa⁷
They phagocytize and destroy pathogens and enhance the anti-infection response of immune cells such as dendritic cells, lymphocytes, and natural killer cells⁷
GM-CSF enhances the chemotactic and phagocytic activity of neutrophils and extends neutrophil survival⁵

Macrophage

macrophage

Macrophage: immune regulator

Macrophages are highly adaptable and dynamic phagocytes that orchestrate the body’s response to infection⁶
They prime and stimulate T cells, promote tissue repair and wound healing, mediate defense against fungal and bacterial pathogens, and produce anti- and pro-inflammatory cytokines⁶
GM-CSF augments the ability of macrophages to phagocytize and destroy bacteria and fungi^1,5

Dendritic Cell

dendritic cell

Dendritic cell: antigen presenter

Dendritic cells are responsible for antigen presentation and immune response regulation⁸
They initiate long-lasting and pathogen-specific immunity⁸
GM-CSF links innate and adaptive immunity by inducing the growth and maturation of antigen-presenting myeloid-derived dendritic cells^1,8

G-CSF=granulocyte-colony stimulating factor; GM-CSF=granulocyte-macrophage colony-stimulating factor.

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IMPORTANT SAFETY INFORMATION AND INDICATIONS

Contraindications

LEUKINE is contraindicated in patients with known hypersensitivity to human granulocyte-macrophage colony stimulating factor such as sargramostim (GM-CSF), yeast-derived products, or any component of LEUKINE.

Warnings and Precautions

Serious hypersensitivity reactions, including anaphylactic reactions, have been reported with LEUKINE. If any serious allergic or anaphylactic reaction occurs, immediately discontinue LEUKINE therapy and institute medical management. Permanently discontinue LEUKINE in patients with serious allergic reactions.
LEUKINE can cause infusion-related reactions, including respiratory distress, hypoxia, flushing, hypotension, syncope and/or tachycardia. Observe closely during infusion, particularly in patients with preexisting lung disease, as dose adjustment or discontinuation may be required.
Do not administer LEUKINE simultaneously with or within 24 hours preceding cytotoxic chemotherapy or radiotherapy or within 24 hours following chemotherapy.
Edema, capillary leak syndrome, pleural and/or pericardial effusion have been reported in patients after LEUKINE administration. LEUKINE should be used with caution and monitored in patients with preexisting fluid retention, pulmonary infiltrates, or congestive heart failure.
Supraventricular arrhythmia has been reported in uncontrolled studies during LEUKINE administration, particularly in patients with a previous history of cardiac arrhythmia. Use LEUKINE with caution in patients with preexisting cardiac disease.
If ANC > 20,000 cells/mm³ or if WBC counts > 50,000/mm³, LEUKINE administration should be interrupted or the dose reduced by half. Twice weekly monitoring of CBC with differential should be performed.
LEUKINE therapy should be discontinued if disease progression is detected during treatment.
Treatment with LEUKINE may induce neutralizing anti-drug antibodies. Use LEUKINE for the shortest duration required.
Liquid solutions containing benzyl alcohol (including LEUKINE Injection) or LEUKINE for Injection reconstituted with Bacteriostatic Water for Injection, USP (0.9% benzyl alcohol) should not be administered to neonates and low birth weight infants.
Concomitant use of drugs that can potentiate the myeloproliferative effects of LEUKINE should be avoided.

Adverse Reactions

Adverse events occurring in >10% of patients receiving LEUKINE in controlled clinical trials and reported in a higher frequency than placebo are:

In Autologous bone marrow transplantation (BMT) patients–asthenia, malaise, diarrhea, rash, peripheral edema, urinary tract disorder
In Allogeneic BMT patients–abdominal pain, chills, chest pain, diarrhea, nausea, vomiting, hematemesis, dysphagia, GI hemorrhage, pruritus, bone pain, arthralgia, eye hemorrhage, hypertension, tachycardia, bilirubinemia, hyperglycemia, increased creatinine, hypomagnesemia, edema, pharyngitis, epistaxis, dyspnea, insomnia, anxiety, high glucose, low albumin
In AML patients–fever, weight loss, nausea, vomiting, anorexia, skin reactions, metabolic laboratory abnormalities, edema

INDICATIONS AND USAGE

LEUKINE is a leukocyte growth factor indicated for the following uses:

LEUKINE is indicated to shorten time to neutrophil recovery and to reduce the incidence of severe, life-threatening, or fatal infections following induction chemotherapy in adult patients 55 years and older with acute myeloid leukemia (AML).
LEUKINE is indicated in adult patients with cancer undergoing autologous hematopoietic stem cell transplantation for the mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis.
LEUKINE is indicated for the acceleration of myeloid reconstitution following autologous peripheral blood progenitor cell (PBPC) or bone marrow transplantation in adult and pediatric patients 2 years of age and older with non-Hodgkin’s lymphoma (NHL), acute lymphoblastic leukemia (ALL) and Hodgkin’s lymphoma (HL).
LEUKINE is indicated for the acceleration of myeloid reconstitution in adult and pediatric patients 2 years of age and older undergoing allogeneic bone marrow transplantation from HLA-matched related donors.
LEUKINE is indicated for the treatment of adult and pediatric patients 2 years and older who have undergone allogeneic or autologous bone marrow transplantation in whom neutrophil recovery is delayed or failed.

Please see full Prescribing Information for LEUKINE.

IMPORTANT SAFETY INFORMATION AND INDICATIONS

Contraindications

LEUKINE is contraindicated in patients with known hypersensitivity to human granulocyte-macrophage colony stimulating factor such as sargramostim (GM-CSF), yeast-derived products, or any component of LEUKINE.

Warnings and Precautions

Serious hypersensitivity reactions, including anaphylactic reactions, have been reported with LEUKINE. If any serious allergic or anaphylactic reaction occurs, immediately discontinue LEUKINE therapy and institute medical management. Permanently discontinue LEUKINE in patients with serious allergic reactions.
LEUKINE can cause infusion-related reactions, including respiratory distress, hypoxia, flushing, hypotension, syncope and/or tachycardia. Observe closely during infusion, particularly in patients with preexisting lung disease, as dose adjustment or discontinuation may be required.
Do not administer LEUKINE simultaneously with or within 24 hours preceding cytotoxic chemotherapy or radiotherapy or within 24 hours following chemotherapy.
Edema, capillary leak syndrome, pleural and/or pericardial effusion have been reported in patients after LEUKINE administration. LEUKINE should be used with caution and monitored in patients with preexisting fluid retention, pulmonary infiltrates, or congestive heart failure.
Supraventricular arrhythmia has been reported in uncontrolled studies during LEUKINE administration, particularly in patients with a previous history of cardiac arrhythmia. Use LEUKINE with caution in patients with preexisting cardiac disease.
If ANC > 20,000 cells/mm³ or if WBC counts > 50,000/mm³, LEUKINE administration should be interrupted or the dose reduced by half. Twice weekly monitoring of CBC with differential should be performed.
LEUKINE therapy should be discontinued if disease progression is detected during treatment.
Treatment with LEUKINE may induce neutralizing anti-drug antibodies. Use LEUKINE for the shortest duration required.
Liquid solutions containing benzyl alcohol (including LEUKINE Injection) or LEUKINE for Injection reconstituted with Bacteriostatic Water for Injection, USP (0.9% benzyl alcohol) should not be administered to neonates and low birth weight infants.
Concomitant use of drugs that can potentiate the myeloproliferative effects of LEUKINE should be avoided.

Adverse Reactions

Adverse events occurring in >10% of patients receiving LEUKINE in controlled clinical trials and reported in a higher frequency than placebo are:

In Autologous bone marrow transplantation (BMT) patients–asthenia, malaise, diarrhea, rash, peripheral edema, urinary tract disorder
In Allogeneic BMT patients–abdominal pain, chills, chest pain, diarrhea, nausea, vomiting, hematemesis, dysphagia, GI hemorrhage, pruritus, bone pain, arthralgia, eye hemorrhage, hypertension, tachycardia, bilirubinemia, hyperglycemia, increased creatinine, hypomagnesemia, edema, pharyngitis, epistaxis, dyspnea, insomnia, anxiety, high glucose, low albumin
In AML patients–fever, weight loss, nausea, vomiting, anorexia, skin reactions, metabolic laboratory abnormalities, edema

INDICATIONS AND USAGE

LEUKINE is a leukocyte growth factor indicated for the following uses:

LEUKINE is indicated to shorten time to neutrophil recovery and to reduce the incidence of severe, life-threatening, or fatal infections following induction chemotherapy in adult patients 55 years and older with acute myeloid leukemia (AML).
LEUKINE is indicated in adult patients with cancer undergoing autologous hematopoietic stem cell transplantation for the mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis.
LEUKINE is indicated for the acceleration of myeloid reconstitution following autologous peripheral blood progenitor cell (PBPC) or bone marrow transplantation in adult and pediatric patients 2 years of age and older with non-Hodgkin’s lymphoma (NHL), acute lymphoblastic leukemia (ALL) and Hodgkin’s lymphoma (HL).
LEUKINE is indicated for the acceleration of myeloid reconstitution in adult and pediatric patients 2 years of age and older undergoing allogeneic bone marrow transplantation from HLA-matched related donors.
LEUKINE is indicated for the treatment of adult and pediatric patients 2 years and older who have undergone allogeneic or autologous bone marrow transplantation in whom neutrophil recovery is delayed or failed.

Please see full Prescribing Information for LEUKINE.

References: 1. Leukine [package insert]. Boston, MA: Partner Therapeutics, Inc.; 2018. 2. Gunsilius E, Gastl G, Petzer AL. Biomed Pharmacother. 2001;55(4):186-194. 3. Kaushansky K. N Engl J Med. 2006;354(19):2034-2045. 4. Kaushansky K. In: Lichtman MA et al, eds. Williams Hematology. 7th ed. New York, NY: McGraw-Hill Companies, Inc.; 2006:chapt 15. 5. Armitage JO. Blood. 1998;92(12):4491-4508. 6. Shapouri-Moghaddam A, Mohammadian S, Vazini H, et al. J Cell Physiol. 2018;233(9):6425-6440. 7. Mayadas TN, Cullere X, Lowell CA. Annu Rev Pathol. 2014;9:181-218. 8. Mellman I. Cancer Immunol Res. 2013;1(3):145-149. 9. Huang F, et al. Am J Respir Crit Care Med. 2011;184:259–268. 10. Standiford LR, et al. Am J Physiol Lung Cell Mol Physiol. 2012;302:L447–L454. 11. Ballinger MN, et al. Am J Respir Cell Mol Biol. 2006;34:766–774.