Leukine sargramostim
Important Safety Considerations

Leukine® (sargramostim) is indicated for the following uses: (i) following induction chemotherapy in older adult patients with acute myelogenous leukemia (AML) to shorten time to neutrophil recovery; (ii) for mobilization and following transplantation of autologous peripheral blood progenitor cells; (iii) for myeloid reconstitution after autologous or allogeneic bone marrow transplantation (BMT); (iv) for use in bone marrow transplantation failure or engraftment delay.
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Leukine in AML

Leukine (sargramostim) is indicated for use following induction chemotherapy in older adult patients with acute myelogenous leukemia (AML) to shorten time to neutrophil recovery and to reduce the incidence of severe and life-threatening infections and infections resulting in death. The safety and efficacy of Leukine have not been assessed in patients with AML under 55 years of age.

The term acute myelogenous leukemia, also referred to as acute non-lymphocytic leukemia (ANLL), encompasses a heterogeneous group of leukemias arising from various non-lymphoid cell lines which have been defined morphologically by the French-American-British (FAB) system of classification.

Leukine® helps neutrophil recovery to reduce the incidence of fatal infections.1 In a pivotal Phase III trial, Leukine:

  • Reduced the incidence of life-threatening, severe, and fatal infections. 1
  • Significantly shortened the median times to neutrophil recovery. 1
  • Adverse events occurring in >10% of AML patients receiving Leukine in controlled clinical trials and reported in a higher frequency than placebo were fever, skin reactions, metabolic disturbances, nausea, vomiting, weight-loss, edema, and anorexia.

In the Phase III clinical trail, the safety and efficacy of Leukine® in the treatment of AML were evaluated in a multi-center, randomized, double-blind placebo-controlled trial of 99 newly diagnosed adult patients, 55–70 years of age, receiving induction with or without consolidation.

*During and within 30 days of study completion.2
The efficacy of Leukine in AML was demonstrated in a pivotal study conducted by Rowe et al 2,4

Significantly fewer fatal infections with LEUKINE*1,2
(during and within 30 days of study completion)

Leukine in AML

There were significantly fewer deaths from infectious causes in the LEUKINE arm (3 versus 11, p=0.02).

*Death during and within 30 days of study completion in a randomized, double-blind study of patients aged 55 to 70 years with de novo AML.1,2 Leukine (250 mcg/m2/day) or placebo was initiated 4 days after the completion of induction chemotherapy and continued until ANC ≥1500/mm3 was attained on 3 consecutive days.1

  • Leukine therapy should be discontinued if disease progression is detected during treatment
  • The majority of deaths in the placebo group were associated with fungal infections with pneumonia as the primary infection.

Leukine shortened time to neutrophil recovery1,2

  • Time to ANC >500/mm3 reduced by 4 days compared with placebo (P=.009)
    • By Day 13 on Leukine®, compared to day 17 for patients receiving placebo
  • Time to ANC >1000/mm3 reduced by 1 week compared with placebo (P=.003)
    • By Day 14 on Leukine®, compared to day 21 for patients receiving placebo
Percent of AML Patients Reporting Events
Events by Body System LEUKINE (n=52) Placebo (n=47) Events by Body System LEUKINE (n=52) Placebo (n=47)
Body, General     Metabolic/Nutritional Disorder    
Fever (no infection) 81 74 Metabolic 58 49
Infection 65 68 Edema 25 23
Weight Loss 81 74 Respiratory System    
Weight Gain 8 21 Pulmonary 48 64
Chills 19 26 Hemic and Lymphatic System    
Allergy 12 15 Coagulation 19 21
Sweats 6 13 Cardiovascular System    
Digestive System     Hemorrhage 29 43
Nausea 58 55 Hypertension 25 32
Liver 77 83 Cardiac 23 32
Diarrhea 52 53 Hypotension 13 26
Vomiting 46 34 Urogenital System    
Stomatitis 42 43 GU 50 57
Anorexia 13 11 Nervous System    
Abdominal distention 4 13 Neuro-clinical 42 53
Skin and Appendages     Neuro-motor 25 26
Skin 77 45 Neuro-psych 15 26
Alopecia 37 51 Neuro-sensory 6 11
Leukine in AML

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References:

  1. LEUKINE® (sargramostim) [package insert]. Genzyme Corporation 2009.
  2. Rowe JM, Rubin A, Mazza JJ, et al. Incidence of infections in adult patients (> 55 years) with acute myeloid leukemia treated with yeast-derived GM-CSF (sargramostim): results of a double-blind prospective study by the Eastern Cooperative Oncology Group. In: Hiddemann W, et al, eds. Acute Leukemias V: Experimental Approaches and Management of Refractory Diseases. Berlin, Germany: Springer-Verlag; 1996:178-184.
  3. Rowe JM. Treatment of acute myeloid leukemia with cytokines: effect on duration of neutropenia and response to infections. Clin Infect Dis. 1998;26:1290-1294.
  4. Rowe JM, Anderson JW, Mazza JJ, et al. A randomized placebo-controlled phase III study of granulocyte-macrophage colony-stimulating factor in adult patients (>55 to 70 years of age) with acute myelogenous leukemia: a study of the Eastern Cooperative Oncology Group (E1490). Blood. 1995;86:457-462.
  5. Nemunaitis J, Rabinowe S, Singer JW, et al. Recombinant granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid cancer. N Engl J Med. 1991;324:1773-1778.
  6. Nemunaitis J, Rosenfeld CS, Ash R, et al. Phase III randomized, double-blind placebo-controlled trial of rhGM-CSF following allogeneic bone marrow transplantation.Bone Marrow Transplant. 1995;15:949-954.
  7. Data on file. Genzyme Corporation.

Indication

Leukine® (sargramostim) is indicated for the following uses: (i) following induction chemotherapy in older adult patients with acute myelogenous leukemia (AML) to shorten time to neutrophil recovery; (ii) for mobilization and following transplantation of autologous peripheral blood progenitor cells; (iii) for myeloid reconstitution after autologous or allogeneic bone marrow transplantation (BMT); (iv) for use in bone marrow transplantation failure or engraftment delay.

Important Safety Information for Leukine® (sargramostim)

  • Leukine is contraindicated in patients with excessive leukemic myeloid blasts in bone marrow or peripheral blood (≥10%); in patients with known hypersensitivity to GM-CSF, yeast-derived products, orany component of Leukine; and for concomitant use with chemotherapy and radiotherapy.
  • Serious allergic or anaphylactic reactions have been reported with Leukine. If any serious allergic or anaphylactic reactions occur, Leukine therapy should be immediately discontinued and appropriate therapy initiated.
  • Liquid solutions containing benzyl alcohol (including liquid Leukine) or lyophilized Leukine reconstituted with Bacteriostatic Water for Injection, USP (0.9% benzyl alcohol) should not be administered to neonates.
  • Leukine should be used with caution and monitored in patients with preexisting fluid retention, pulmonary infiltrates, or congestive heart failure, respiratory symptoms or disease; cardiac symptoms or disease; and renal or hepatic dysfunction.
  • Edema, capillary leak syndrome, pleural and/or pericardial effusion, sequestration of granulocytes in the pulmonary circulation, and dyspnea have been reported in patients after Leukine administration. Occasional transient supraventricular arrhythmia has been reported during Leukine administration. Leukine has induced the elevation of serum creatinine or bilirubin and hepatic enzymes in some patients. Monitoring of renal and hepatic function in patients with preexisting renal or hepatic dysfunction is recommended at least every other week during Leukine administration.
  • Adverse events occurring in >10% of patients receiving Leukine in controlled clinical trials and reported in a higher frequency than placebo were: in AML patients – (fever, skin reactions, metabolic disturbances, nausea, vomiting, weight-loss, edema, anorexia); in Autologous BMT patients – (asthenia, malaise, diarrhea, rash, peripheral edema, urinary tract disorder); and 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 BUN, and high cholesterol).
  • If ANC > 20,000 cells/mm3 or if platelet counts > 500,000/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.
  • Drugs that can increase WBCs, such as lithium and corticosteroids, should be used with caution while receiving Leukine. Interactions between Leukine and other drugs have not been fully evaluated.

Please see full Prescribing Information.

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