Researchers may have uncovered a close link between genetic factors and racial disparities in pediatric patients with acute myeloid leukemia (AML), according to new findings presented by Lamba et al at the 2023 American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 386).
Background
Response to chemotherapy treatment commonly used to treat AML and drug activation may be influenced by a patient’s genes. The multigene ACS10 score is capable of accounting for variability across multiple genes simultaneously and combining 10 genetic factors into a single metric. Previous studies had indicated that low ACS10 scores and high AML mortality rates may be especially prevalent among Black pediatric patients in Africa.
“Incorporating the ACS10 score into diagnostic processes can help us use our chemotherapy options more strategically,” explained lead study author Jatinder K. Lamba, PhD, Professor in the College of Pharmacy and Associate Dean for Research and Graduate Education at the University of Florida as well as a member of the University of Florida Health Cancer Center. “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,” she added.
Study Methods and Results
In the new study, the researchers analyzed the comprehensive genetic information of 86 Black patients and 359 White patients who participated in two AML clinical trials and were treated with one of three regimens as initial therapy: high-dose cytarabine, daunorubicin, and etoposide; low-dose cytarabine, daunorubicin, and etoposide; or clofarabine and cytarabine. The researchers used the ACS10 score to help elucidate the genetic drivers of racial disparities and inform treatment decisions.
Although the researchers found no statistically significant differences between Black patients and White patients in terms of various measures of treatment response, survival, and relapse; they identified significant differences after assessing race and ACS10 scores. The Black patients who presented with low ACS10 scores had significantly greater outcomes when they received the high-dose or clofarabine and cytarabine regimen compared with when they received the low-dose regimen.
“If you give patients with a lower ACS10 score an augmented therapy, you can really significantly improve their outcomes,” detailed Dr. Lamba.
Further, the researchers discovered a substantial racial gap in the distribution of ACS10 scores, where 73% of the Black patients and 30% of the White patients had low ACS10 scores. This difference, combined with the relationship between low ACS10 scores and poor responses to the low-dose regimen were potentially responsible for a portion of the racial disparities in survival among patients with AML.
Conclusions
The researchers concluded that using the ACS10 score to optimize treatment strategies in this patient population may lead to improved outcomes, especially among Black pediatric patients. The metric may provide new evidence that some induction regimens could result in more positive outcomes compared with other regimens for pediatric patients with lower ACS10 scores. The researchers noted that further studies should be conducted in Africa to observe whether tailoring treatments based on the ACS10 score could help improve outcomes.
Although the panel testing protocol for ACS10 scores is not readily available in most clinics, the researchers noted that routine diagnostic tests already include the genetic features that are combined for the ACS10 score and that incorporating the ACS10 score into diagnostic processes could be a simple, low-cost addition to the existing testing protocol.
Disclosure: For full disclosures of the study authors, visit ash.confex.com.
