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Using Polygenic ACS10 Score to Guide Treatment Decisions in AML

By: Joseph Fanelli
Posted: Tuesday, March 8, 2022

According to findings presented in the Journal of Clinical Oncology, patients with acute myeloid leukemia (AML) who have a low 10-single nucleotide polymorphisms (SNP) cytarabine_SNP (ACS10) score may have significantly worse outcomes when treated with standard regimens when compared with alternative treatments. Augmentation treatment with either high doses of cytarabine or the addition of gemtuzumab ozogamicin may improve patient outcomes for those with low ACS10 scores, concluded Jatinder K. Lambda, PhD, of the University of Florida, Gainesville, and colleagues.

“Our comprehensive approach not only provides a unique ACS10 score of prognostic significance that can predict poor outcome in AML, but [it] suggests that alternative treatment strategies with either high-dose [cytarabine] or addition of gemtuzumab ozogamicin are more suitable strategies for patients with detrimental low-ACS10 score,” the authors stated.

In this study, the authors analyzed the cytarabine-pathway genes from patients enrolled in the multicenter-AML02 trial (166 patients). Multi-SNP predictor modeling was used to develop ACS10 scores using the top SNPs predictive of measurable residual disease and event-free survival. ACS10 scores were measured by association with outcomes in each clinical trial arm. From the AML02 cohort, patients received standard low-dose cytarabine (n = 91) and augmented high-dose cytarabine (n = 75). From the AAML0531 trial, the regimen featured standard cytarabine, daunorubicin, and etoposide (465 patients) and augmented daunorubicin and etoposide plus gemtuzumab ozogamicin (466 patients).

The authors found that patients treated with standard low-dose cytarabine who had low ACS10 scores reported significantly worse event-free survival and overall survival rates than those patients with high ACS10 scores. This finding was validated in the group given standard daunorubicin and etoposide, with patients who had low ASC10 scores having poorer outcomes than those with high ACS10 scores.

Within the augmented groups—augmented high-dose cytarabine and daunorubicin and etoposide plus gemtuzumab ozogamicin—event-free survival and overall survival rates did not differ between those who had low or high scores of ASC10. In both groups, those with low ASC10 consistency demonstrated a 10% improvement in 5-year event-free survival with augmented therapy than with standard therapy.

Disclosure: For full disclosures of the study authors, visit ascopubs.org.


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