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 Engraftment Delay or Failure

Based on the safety and efficacy demonstrated in the following trial, Leukine® (sargramostim) was approved for autologous and allogeneic bone marrow transplantation failure and engraftment delay. Leukine is the only colony-stimulating factor with this indication.

In this study — designed to determine whether survival could be improved following engraftment failure or delay in AuBMT and AlloBMT — 140 Leukine -treated patients from 35 institutions were compared with 103 historical control patients. Survival endpoints were more favorable in patients who received Leukine compared with historical controls:

  • The 100-day survival rate following either autologous or allogeneic BMT was higher in the patients treated with Leukine (P <.05)
  • Median survival was nearly tripled in the Leukine group (P <.05)
  • Leukine was shown to be well tolerated and did not have adverse effects on the resolution of infection
  • 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.

The detailed results are provided below.

Median survival in patients receiving Leukine nearly tripled1,7:

Survival Following Engraphment Failure or Delay

 Chart 8

  • AuBMT — Leukine patients had a median survival of 474 days compared with a median survival of only 161 days in the historical control group (P <.05)
  • AlloBMT — Leukine patients had a median survival of 97 days compared with a median survival of only 35 days in the historical control group (P <.05)
  • Improvement in survival was better in patients with fewer impaired organs
  • Edema, capillary leak syndrome, pleural and/or pericardial effusion, supraventricular tachycardia, sequestration of granulocytes in the pulmonary circulation, and dyspnea have been reported in patients after Leukine administration. Leukine has induced the elevation of serum creatinine or billirubin 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.

In delayed engraftment or graft failure following AuBMT and AlloBMT, Leukine reduced death from infection by 53%1,7

Infection Related Mortality at 100 Days

 

Data on file. Leukine (sargramostim) package insert. Bayer HealthCare Pharmaceuticals, 2002.

  • The infection-related mortality at 100 days in the placebo group was 47% compared with only 22% in the Leukine group (P=.05)
  • 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.

Use in Autologous Bone Marrow Transplantation (AuBMT)

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.