Important Safety Considerations
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 or any component of Leukine, and for concomitant use with chemotherapy and radiotherapy. View additional Important Safety Information. View Indications.

Leukine® in AML

For patients 55 years and older with AML following induction chemotherapy.

Leukine® goes beyond neutrophil recovery to reduce the incidence of fatal infections.1,2 In a pivotal Phase III trial Leukine.

  • Reduced the incidence of early death associated with fungal infections, including deaths due to Aspergillus and Candida1-3 *
  • Reduced the incidence of life-threatening, severe, and fatal infections1,2 *
  • Shortened time to neutrophil recovery1,2 *
  • Had an adverse event profile similar to placebo1
  • 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.

*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)

*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
  • There were significantly fewer deaths from infectious causes in the LEUKINE arm (3 versus 11, p=0.02).
  • The majority of deaths in the placebo group were associated with fungal infections with pneumonia as the primary infection.

In the pivotal AML trial:

  • Reduced the incidence of life-threatening, severe, and fatal infections1,2 * 
    • Significantly fewer severe and life-threatening infections (all causes) (36% with placebo vs 10% with Leukine3; P=.002) in the pivotal AML trial2

LEUKINE improved the probability of overall survival †4
(intent-to-treat population)

† In the randomized, double-blind study of patients aged 55 to 70 years with de novo AML, 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

  • Study was not sized to assess overall survival1

Leukine shortened time to neutrophil recovery1,2

  • Time to ANC >500/mm3 reduced by 4 days compared with placebo (P=.009)
  • Time to ANC >1000/mm3 reduced by 1 week compared with placebo (P=.003)

Indication

Leukine® 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 Considerations

  • 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, or any 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.

Please see full Prescribing Information.

To report suspected adverse events, contact Genzyme Corporation at 1-888-4RX-LEUKINE or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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.