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High expression of VLA-4 associated with better outcome in children with AML
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High very late antigen-4 expression in children with acute myeloid leukemia predicted better outcome consisting of reduced relapse rate and better DFS, according to a prospective analysis of a Children’s Oncology Group study.
The researchers, led by Roland B. Walter, MD, of Fred Hutchinson Cancer Research Center, examined very late antigen-4 (VLA-4) expression in 216 patients enrolled in a phase-3 pilot study. The study was designed to examine the safety and efficacy of gemtuzumab ozogamicin (Mylotarg, Wyeth) when added to chemotherapy.
VLA-4 expression varied by more than 35-fold with positive skewing.
Patients with high VLA-4 expression were younger (aged 7.1 years) than patients with low VLA-4 expression (aged 12.1 years; P<.001). FLT3 internal tandem duplication prevalence was lower among the high expression group (4%) vs. the lower expression group (21%; P<.001).
Additionally, patients with high VLA-4 expression were more likely to have extramedullary disease (16%) than those with low expression (5%; P=.013).
There were similar complete remission rates (P=.137) and rates of incidence of minimal residual disease (P=.7) for patients with high and low VLA-4 expression.
Patients with high expression had a lower three-year relapse rate (24%) vs. the low expression group (44%; P=.011) and higher DFS rate (67%) vs. those with low VLA-4 expression (48%; P=.023). OS was similar between groups.
In multivariate analysis, low VLA-4 expression was an independent prognostic factor for higher relapse rates (HR=2.77; 95% CI, 1.28-5.97) and shorter DFS (HR=1.98; 95% CI, 1.04-3.78).
In subgroup analysis, after three years, relapse rates were lower for patients with high VLA-4 expression (26%) vs. low VLA-4 expression (61%; P=.009). DFS rates were higher for the high VLA-4 expression group (69%) than for the low VLA-4 expression group (34%; P=.011).
In multivariate analysis, low expression of VLA-4 remained an independent prognostic factor for higher relapse rates (HR=6.86; 95% CI, 2.05-22.9) and lower DFS rates (HR=5.05; 95% CI, 1.72-14.8).
The findings of this analysis revealed significant heterogeneity of VLA-4 expression in children with AML, according to the researchers.
“If the usefulness of VLA-4 expression for prognostication in patients without identifiable cytogenetic or molecular risk factors is confirmed, it may be integrated into the design of risk-adapted treatment strategies, for example, in upcoming COG trials,” they wrote.
For more information:
- Walter RB. J Clin Oncol. 2010;doi:10.1200/JCO.2009.27.5693.