ASH: Mylotarg Boosts AML Disease-Free Survival

December 12, 2006

ORLANDO -- Antibody-directed therapy added to induction chemotherapy for acute myeloid leukemia (AML) improved disease-free survival without major added toxicity, international researchers reported here.

ORLANDO, Dec. 9 -- Antibody-directed therapy added to induction chemotherapy for acute myeloid leukemia (AML) improved disease-free survival without major added toxicity, international researchers reported here.

Preliminary results from a study of 1,113 patients younger than 60 who were randomized to standard induction chemotherapy regimens with our without the addition of Mylotarg (gemtuzumab ozogamicin) showed that patients who received the antibody had significantly better disease-free survival, said Alan K. Burnett, M.D., of Cardiff University in Wales, at the of the American Society of Hematology meeting here.

"This is the first example of antibody-directed therapy in cancer," Dr. Burnett said. "It's the first randomized trial of Mylotarg, and it does indeed seem to have an advantage in reducing the relapse risk without increasing toxicity."

Mylotarg is an immunoconjugate consisting of a monoclonal antibody directed against the CD33 receptor on leukemia cells and an antitumor antibiotic.

Dr. Burnett and Danish colleagues enrolled the 1,113 patients in a randomized controlled trial in which patients were assigned to conventional chemotherapy with either danorubicin plus Ara-C (cytarabine), the same two drugs plus etoposide, or FLAG-IDA, a combination fludarabine, Ara-C, granulocyte colony stimulating factor and idarubicin.

In addition, half the patients were randomized to receive Mylotarg at 3 mg/m2 on day one of each course of therapy.

The median patient age was 49 (range 0-71 years). The gender breakdown was 592 male and 521 female. Most of the patients (1,025) had de novo disease and 88 had secondary diseases.

In all, 95% of patients had WHO performances scores less
than 2.

The investigators found that the overall remission rates were similar between the Mylotarg and no-Mylotarg groups, at 84% and 86%, respectively, and no differences in complete remission (85% in each group) induction deaths, or resistant disease.

There was a modest increase in mucositis in the Mylotarg group during the first course of chemotherapy only (P=0.04) and increased liver enzymes (P=0.002 for AST, and P=0.03 for ALT), but no difference in bilirubin grades, and grade 3-4 liver toxicities were similar.

Patients in the Mylotarg arm also used more platelets (19 units versus 14, P