Researchers from France have identified a potential predictor of treatment outcomes in patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) receiving azacitidine therapy.
According to the study recently published in the British Journal of Haematology, half of the patients had deficient cytidine deaminase (CDA) activity (cutoff of 2 UA/mg)—an enzyme responsible for detoxifying azacitidine in the liver. The proportion of patients with deficient CDA was lower among patients with MDS (34%) compared with patients with AML (67%).
In patients with high-risk MDS, CDA deficiency correlated with longer landmark overall survival, showing a median overall survival of 14 months compared with 8 months in patients with normal CDA activity (P =.03). However, in patients with AML, CDA deficiency did not demonstrate a similar impact on overall survival.
“This non-interventional, observational, monocentric and retrospective study suggests that MDS patients with CDA poor metaboliser status have a better response, survival and total number of courses when treated with azacitidine,” the researchers said. “CDA could next be used in a dosing algorithm to tailor azacitidine dosing.”
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The study has also demonstrated a high variability in CDA activity at the population level, with a geometric coefficient of variation estimated at 68%. Univariate analysis identified factors such as absolute neutrophil count, white blood cell count, and pathology type as influencing serum CDA activity. In multivariate analysis, both absolute neutrophil count and pathology types were strong predictors of CDA activity.
Furthermore, in a subset analysis of 66 patients with complete blast count monitoring, the researchers noted a significant difference in bone marrow blasts between poor metabolizers and extensive metabolizers.
The data also suggested that delaying azacitidine treatment did not correlate with reduced efficacy.
The study enrolled 104 adults with high-risk MDS (51%) and AML (49%). The median overall survival was 13 months for patients with high-risk MDS and 15 months for patients with AML.
Reference
Donnette M, Hamimed M, Ciccolini J, et al. Cytidine deaminase status as a marker of response to azacytidine treatment in MDS and AML patients. Br J Haematol. Published online September 10, 2023. doi:10.1111/bjh.19096
