Gemtuzumab Ozogamicin Reduces Minimal Residual Disease in Children With High-Risk Acute Myeloid Leukemia
Combining gemtuzumab ozogamicin (Mylotarg) with conventional chemotherapy may improve the outcome of bone marrow transplantation for some children battling high-risk acute myeloid leukemia (AML), according to a study led by St. Jude Children’s Research Hospital. The results appear in the November 15 issue of the journal Cancer.
For young AML patients with suitable bone marrow donors, transplantation offers the best chance of a cure. Being free of even low levels of detectable cancer cells prior to transplantation is associated with better patient survival. This analysis found that combination therapy helped to eliminate minimal residual disease in young AML patients who initially had a poor response to chemotherapy. By reducing minimal residual disease levels prior to transplantation, it is likely that gemtuzumab ozogamicin contributed to the favorable outcome of these patients, researchers said.
‘Strong Case’ for Gemtuzumab
Gemtuzumab was approved by the U.S. Food and Drug Administration in 2000 for the treatment of AML in adults and was voluntarily withdrawn in 2010 following questions about its safety and efficacy. Since then several studies conducted while the drug was authorized reported promising results in adults with AML. Those reports prompted this current analysis of pediatric AML patients who received gemtuzumab ozogamicin in a clinical trial conducted while the drug was available.
Researchers said the results add to evidence that both adults and children with AML may benefit from treatments that use a similar mechanism as gemtuzumab to combat AML. The drug was not associated with severe toxicity in this or other recent studies.
Unlike traditional chemotherapy that kills rapidly dividing cells, both malignant and healthy, gemtuzumab works by targeting a protein carried on the surface of about 90% of AML cells. Work has begun on new strategies, including antibody-based therapies, that target the same AML surface protein, said the study’s senior author Jeffrey Rubnitz, MD, PhD, a member of the St. Jude Department of Oncology.
“Currently there are few options for AML patients who relapse or do not respond to conventional therapy,” said first author Carol O’Hear, MD, PhD, a St. Jude postdoctoral oncology fellow. Dr. Rubnitz added, “The results of this and earlier studies make a strong case that some patients benefit from this targeted therapy, which has us looking for new ways to take aim at the same protein.”
Study Details
This study involved a subset of patients enrolled in a clinical trial of pediatric AML called AML02. Altogether, 232 children with AML enrolled in the 6-year, multicenter trial that ended in 2008. A total of 46 patients received gemtuzumab alone or in combination with conventional chemotherapy.
For this analysis, researchers wanted to know if gemtuzumab was associated with reduced minimal residual disease. Patients were considered free of minimal residual disease if less than one cancer cell could be detected in 1,000 normal bone marrow cells.
Minimal Residual Disease
Seventeen patients received gemtuzumab alone when minimal residual disease was detected after two rounds of chemotherapy with cytarabine, daunorubicin, and etoposide. After gemtuzumab treatment, leukemia declined in 14 of the 17 patients and fell to undetectable levels in 13 patients.
An additional 29 patients received gemtuzumab as part of their second round of three-drug chemotherapy. All had levels of residual disease that indicated a poor initial response to chemotherapy alone, including nine with minimal residual disease levels of 25% or more. Residual disease fell to undetectable levels in four of the nine patients following combination therapy.
Malignant cells fell to undetectable levels in 45%, or 9 of the remaining 20 patients whose second round of treatment included gemtuzumab ozogamicin plus chemotherapy. The patients all had minimal residual disease of between 1% and 25% after the first round of chemotherapy.
Survival Outcomes
The overall 5-year survival level of the 20 patients was 55%, compared to 36% for 22 patients with similar minimal residual disease who received chemotherapy alone. The survival difference between the two groups was not statistically significant, but investigators said the results point to a possible benefit of gemtuzumab ozogamicin treatment for some pediatric AML patients whose cancer remained following chemotherapy.
The 22 patients were treated early in AML02, before the protocol was revised to expand the use of gemtuzumab ozogamicin. The revision followed evidence that the drug was well tolerated by the young AML patients.
The study was supported in part by a grant (CA02176530) from the National Cancer Institute at the National Institutes of Health and ALSAC.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
