Leukine

Clinical Pharmacology

font size

Clinical Pharmacology

Leukine

Antibody Formation

Serum samples collected before and after Leukine treatment from 214 patients with a variety of underlying diseases have been examined for the presence of antibodies. Neutralizing antibodies were detected in 5 of 214 patients (2.3%) after receiving Leukine by continuous IV infusion (3 patients) or subcutaneous injection (2 patients) for 28 to 84 days in multiple courses. All 5 patients had impaired hematopoiesis before the administration of Leukine and consequently the effect of the development of anti-GM-CSF antibodies on normal hematopoiesis could not be assessed. Drug-induced neutropenia, neutralization of endogenous GM-CSF activity and diminution of the therapeutic effect of Leukine secondary to formation of neutralizing antibody remain a theoretical possibility.

CLINICAL EXPERIENCE

Acute Myelogenous Leukemia

The safety and efficacy of Sargramostim in patients with AML who are younger than 55 years of age has not been determined. Based on phase II data suggesting the best therapeutic effects could be achieved in patients at highest risk for severe infections and mortality while neutropenic, the phase III clinical trial was conducted in older patients. 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.⁶ A combination of standard doses of daunorubicin (days 1-3) and ara-C (days 1-7) was administered during induction and high dose ara-C was administered days 1-6 as a single course of consolidation, if given. Bone-marrow evaluation was performed on day 10 following induction chemotherapy. If hypoplasia with <5% blasts was not achieved, patients immediately received a second cycle of induction chemotherapy. If the bone marrow was hypoplastic with <5% blasts on day 10 or 4 days following the second cycle of induction chemotherapy, Leukine (250 mcg/m²/day) or placebo was given IV over 4 hours each day, starting 4 days after the completion of chemotherapy. Study drug was continued until an ANC 31500/mm³ for three consecutive days was attained or a maximum of 42 days. Leukine or placebo was also administered after the single course of consolidation chemotherapy if delivered (ara-C 3-6 weeks after induction following neutrophil recovery). Study drug was discontinued immediately if leukemic regrowth occurred.

Leukine significantly shortened the median duration of ANC <500/mm³ by 4 days and <1000/mm³ by 7 days following induction (see table below). 75% of patients receiving Leukine achieved ANC >500/mm³ by day 16 compared to day 25 for patients receiving placebo. The proportion of patients receiving 1 cycle (70%) or 2 cycles (30%) of induction was similar in both treatment groups; Leukine significantly shortened the median times to neutrophil recovery whether one cycle (12 versus 15 days) or two cycles (14 versus 23 days) of induction chemotherapy was administered. Median times to platelet (>20,000/mm³) and RBC transfusion independence were not significantly different between treatment groups.

During the consolidation phase of treatment, Leukine did not shorten the median time to recovery of ANC to 500/mm³ (13 days) or 1000/mm³ (14.5 days) compared to placebo. There were no significant differences in time to platelet and RBC transfusion independence.

Hematological Recovery: Induction

Brand Name: Leukine
Generic Name: Sargramostim