Researchers affiliated with the Children’s Oncology Group have reported that addition of a single dose of gemtuzumab ozogamicin (Mylotarg®) to standard induction may improve outcomes of children with newly diagnosed acute myeloid leukemia (AML). The details of this pilot study were presented at the 50^th annual meeting of the American Society of Hematology on December 8, 2008 in San Francisco.[1] 

Gemtuzumab is a monoclonal antibody linked to a toxin called calicheamycin. The monoclonal antibody is directed at CD33, which is present in 80-90% of AML cells but is not present on the normal hematopoietic stem cell. Thus, the antibody-toxin conjugate can selectively kill leukemia cells. The primary toxicity of this agent is veno-occlusive disease (VOD) of the liver, presumably because there are CD33-positive cells in the liver. Gemtuzumab was approved by the U.S. Food and Drug Administration in 2000 for the treatment of patients with AML over the age of 60 who had failed initial treatment but is not yet approved in children.

A previous study of gemtuzumab in 16 children with relapsed AML found that eight had a reduction in bone marrow blasts to less than 5%, but only five of these had complete recovery of platelets.[2] Researchers at the Fred Hutchinson Cancer Research Center and six other cancer centers have reported a 28% combined partial and complete remission rate in children with relapsed or refractory AML with single-agent gemtuzumab.[3] Another study from Germany showed single-agent gemtuzumab produced responses but no complete remissions in 12 refractory children with AML.[4] Gemtuzumab has also been evaluated as post-transplant treatment in children with AML receiving reduced-intensity allografts.[5]

The current study include 340 patients ages 1 month to 21 years with de novo AML.  Patients received two induction courses and three intensification courses. Gemtuzumab was added to the second intensification course, which also contained mitrozantrone and cytarabine. High-risk patients received only one course of intensification followed by an allogeneic stem cell transplant following a busulfan-cyclophosphamide regimen if a donor was available. Median follow-up was 775 days. The major findings of this study were as follows:

• After the first induction, the CR rate was 83%.
• After the second induction, the CR rate was 87%.
• Three-year EFS was 49%.
• Three-year OS was 63%.
• Treatment-related mortality was 9% after the first induction and 7% after the second induction regimen.
• The risk of relapse in patients with a stem cell donor was 12% compared with 39% for those without a donor on an intent-to-treat analysis.
• The incidence of VOD was 5%.

These authors stated: “Overall, AAMLO3P1 therapy shows a continued historical trend for improved OS and EFS when compared to the previous COG AML trial (CCG-2961).”

Comments: This is the first report on gemtuzumab in children with newly diagnosed AML.     

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