(ChemotherapyAdvisor) – The antibody conjugate gemtuzumab ozogamicin (GO) reduces relapse rates and might improve 3-year survival rates among older patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS), according to a randomized Phase 3 study, published in the Journal of Clinical Oncology.
“Adding GO (3 mg/m2) to induction chemotherapy reduces relapse risk and improves survival with little increase to toxicity,” reported lead author Alan K. Burnett, MD, of the Cardiff University School of Medicine, Cardiff, United Kingdom, and coauthors. “There was no interaction with other treatment interventions.”
At a median follow-up of 30 months (range, 5.5 to 54.6 months), cumulative relapse incidence was lower among patients receiving GO (68% vs 76%; HR, 0.78; 95% CI, 0.66-0.93; P=0.007). GO was also associated with a marginally-significantly superior 3-year survival rate (25% vs 20%; HR, 0.87; 95% CI, 0.76-1.00; P=0.05).
A separately-conducted meta-analysis of data for 2,228 UK patients showed that GO is associated with significant improvements in relapse rates (P=0.002) and overall survival (OS; P=0.02) the authors noted (HR, 0.82; 95% CI, 0.72-0.93; P=0.002).
The clinical trial enrolled 1,115 patients at 149 hospitals in the United Kingdom and Denmark; all were previously-untreated patients with AML or high-risk MDS, and the median age of participants was 67 years.
Untreated, MDS can evolve into AML.
“The overall response rate was 69% (complete remission [CR], 60%; CR with incomplete recovery [CRi], 9%), with no difference between GO (70%) and no GO (68%) arms,” the authors reported. “There was no difference in 30- or 60-day mortality and no major increase in toxicity with GO.”
A previous trial by the same researchers showed that survival among younger patients might similarly improve with the addition of GO to induction chemotherapy.
GO was voluntarily withdrawn from the market in the United States in 2010, following the SWOG0106 trial of younger patients found no OS advantage and “concern that early mortality was significantly worse in the GO (6 mg/m2) than the control arm (5.8% vs 0.8%),” the authors noted.
“However, an induction death rate of 5% to 7% is a feature of most induction therapies in patients of that age, and this was not observed in our large total experience of more than 2,200 randomly assigned patients,” the authors noted.
They argued that it is “clear that GO at 3 mg/m2 administered simultaneously with daunorubicin (50 mg/m2) as part of induction therapy is safe, significantly reduces relapse risk, and improves OS.”
Dr. Burnett is a paid consultant for Pfizer, which markets GO as Mylotarg.