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)
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|
|Weight Loss||81||74||Respiratory System|
|Chills||19||26||Hemic and Lymphatic System|
|Skin and Appendages||Neuro-motor||25||26|
- LEUKINE® (sargramostim) [package insert]. Genzyme Corporation 2009.
- 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.
- 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.
- 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.
- 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.
- 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.
- Data on file. Genzyme Corporation.