Share

|

|

|

  • News & Insights
  • >
  • Pharmacogenomic-guided induction therapy might reduce pediatric AML racial disparities
Childhood friendship between two girls

Pharmacogenomic-guided induction therapy might reduce pediatric AML racial disparities

By Lynda Williams, medwireNews Reporter

medwireNews: Using a pharmacogenomic strategy to guide choice of induction therapy for acute myeloid leukaemia (AML) might help overcome the disparity in outcomes between Black and White children, suggests research published in JAMA Network Open.

“Disparities in outcomes among individuals with [AML] have been observed across age groups, with Black patients experiencing poorer prognosis compared with their White counterparts among children, adolescents and young adults, and adults”, explain Jeffrey Rubnitz (St Jude Children’s Research Hospital, Memphis, Tennessee, USA) and co-authors.

The researchers hypothesized that it would be possible to overcome this disparity by using the ACS10 pharmacogenomic score, based on 10 single nucleotide variants that characterize intracellular levels of the enzyme that activates cytarabine. To investigate, they conducted a comparative effectiveness analysis using data from the AML02 trial, which randomly assigned patients to receive standard low-dose or augmented high-dose cytarabine-based induction therapy and the AML08 trial of augmented high-dose cytarabine-based induction therapy.

The team collated information from 86 Black children (62.8% boys, mean age 8.8 years) and 359 White children (52.6% boys, mean age 9.1 years). These groups had comparable average leukocyte counts of 52,600 and 54,500 cells/μL, respectively.

Five-year event-free survival (EFS) was similar among Black and White patients (58.3 vs 58.2%), as was overall survival (OS; 63.8 vs 69.4%) and the cumulative incidence of relapse (26.0 vs 26.1%).

This was despite Black patients being more likely to have core-binding factor AML (31.4 vs 20.1%), which is associated with a favorable outcome, the researchers say. The 5-year EFS of Black and White patients did not significantly differ between those with (84.6 vs 88.6%) or without (53.7 vs 54.9%) this type of AML, the team found.

However, Black patients without core-binding factor AML who received standard induction therapy had significantly worse 5-year EFS than their White counterparts (25 vs 56%). This EFS discrepancy was no longer present when Black and White patients both received augmented induction therapy (50 vs 48%).

ACS10 scores were available for 81.4% of Black patients and 76.0% of White patients and there was a significant difference in the distribution of ACS10 scores by race. Specifically, 72.9% of Black patients had a low ACS10 score compared with 30.0% of White patients.

There were no significant differences in EFS between Black and White patients with low ACS10 scores or between Black and White participants with high ACS10 scores, the researchers say.

But among patients given standard induction therapy, those with low ACS10 scores had significantly poorer 5-year EFS than those with high ACS10 scores (42.4 vs 70.0%); a disparity that was not present among patients who were given augmented high-dose induction therapy (60.6 vs 54.8%).

Rubnitz et al admit: “Given that current clinical trials for pediatric AML do not incorporate high-dose cytarabine or clofarabine during induction therapy, it is not feasible to conduct a validation study.”

Nevertheless, they conclude: “The associations between race, pharmacogenomics, treatment intensity, and outcome suggest that racial disparities in outcome are associated with variations in pharmacogenomics.

“We propose that future studies should include the nonrandomized tailoring of induction regimens to pharmacogenomic parameters to improve the outcome of Black and White patients and serve as a pivotal bridge in addressing the racial gap in AML treatment outcomes.”

News stories are provided by medwireNews, which is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group 

This independent news story was supported by an educational grant from L’Institut Servier, Suresnes, France.

JAMA Netw Open 2024; doi:10.1001/jamanetworkopen.2024.11726

Image credit: © Montsera Production / pixabay.com

 

Don’t fall behind!

Get the latest headlines – in your specialties of choice – delivered straight to your inbox.

Showcase

MEET THE SENIOR TEAM

Lucy Piper

medwireNews Bureau Chief