In a new study, a multi-gene metric known as ACS10, which accounts for variability in multiple genes simultaneously, revealed a close link between genetic factors and racial disparities in pediatric acute myeloid leukemia (AML) outcomes. Researchers say using the metric to optimize treatment approaches for each patient could potentially lead to better outcomes, particularly among Black children.
Because the chemotherapy drugs used to treat AML are activated inside the body, a person’s genes can influence drug activation and the response to treatment. The new study bolsters evidence that the ACS10 score, which combines 10 genetic factors into a single metric, can be used to help elucidate genetic drivers of racial disparities and inform treatment decisions. Researchers say it provides new evidence that some induction regimens result in better outcomes than other regimens for people with lower ACS10 scores, a status that is more common among Black patients.
“Incorporating the ACS10 score into diagnostic processes can help us use our chemotherapy options more strategically,” said Jatinder K. Lamba, Ph.D., associate dean for research and graduate education and professor in the University of Florida College of Pharmacy, and the study’s lead author. “We are always running after new drugs, but we see that there are smarter ways to use existing drugs. I’m hoping this [metric] will go into standard guidelines, so that we can use the genetics to inform the regimen.”
Since routine diagnostic tests already include the genetic features that are combined for the ACS10 score, Lamba said that incorporating ACS10 scores into diagnostic processes would be an easy addition to the existing testing and should be feasible to do at low cost.
For the study, the researchers analyzed data from two previous AML clinical trials that together included 86 Black patients and 359 white patients. The trials included comprehensive genetic information for each patient and involved three different treatment regimens as initial therapy: low-dose cytarabine, daunorubicin, and etoposide (LDAC), higher doses of these same drugs (HDAC), or clofarabine and cytarabine (Clo/AraC).
The results showed no significant differences between Black and white patients overall in terms of various measures of response to treatment, survival, and relapse. However, significant differences emerged when researchers took both race and ACS10 scores into account. Black patients with low ACS10 scores had significantly better outcomes when they received the HDAC or Clo-AraC regimen than when they received LDAC.
“If you give patients with a lower ACS10 score an augmented therapy, you can really significantly improve their outcome,” said Lamba, who is co-leader of the UF Health Cancer Center’s Cancer Targeting and Therapeutics research program. The researchers also found a substantial racial gap in the distribution of ACS10 scores. While just 30% of white patients had a low ACS10 score, 73% of Black patients did. This difference, combined with the relationship between low ACS10 scores and poor response to LDAC treatment, likely explains some of the racial disparities in AML survival that have been reported previously.
Other studies suggest that low ACS10 scores are especially prevalent among Black children in Africa, where AML mortality rates are persistently high. Lamba suggested that further studies should be conducted in Africa to see if tailoring treatments based on this metric could help to improve outcomes.
Although the panel testing protocol for ACS10 scores is not readily available in most clinics today, researchers said it should be feasible to deploy relatively quickly since the individual components of the test are available.
-American Society of Hematology
Francisco Marchi, Richard Marrero, Pharm.D., and Nam Nguyen, Pharm.D., who train under Jatinder Lamba, Ph.D., received abstract achievement awards at the 2023 American Society of Hematology Annual Meeting.