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Randomized Controlled Trial
. 2024 May 1;7(5):e2411726.
doi: 10.1001/jamanetworkopen.2024.11726.

Pharmacogenomics, Race, and Treatment Outcome in Pediatric Acute Myeloid Leukemia

Jatinder K Lamba  1   2   3 , Richard Marrero  1 , Huiyun Wu  4 , Xueyuan Cao  5 , Phani Krisha Parcha  1 , Seth E Karol  6 , Hiroto Inaba  6 , Dennis John Kuo  7 , Barbara A Degar  8   9 , Kenneth Heym  10 , Jeffrey W Taub  11 , Norman J Lacayo  12   13 , Ching-Hon Pui  6 , Raul C Ribeiro  6 , Stanley B Pounds  4 , Jeffrey E Rubnitz  6
Affiliations
Randomized Controlled Trial

Pharmacogenomics, Race, and Treatment Outcome in Pediatric Acute Myeloid Leukemia

Jatinder K Lamba et al. JAMA Netw Open. .

Erratum in

  • Error in Byline.
    [No authors listed] [No authors listed] JAMA Netw Open. 2025 Feb 3;8(2):e250502. doi: 10.1001/jamanetworkopen.2025.0502. JAMA Netw Open. 2025. PMID: 39913144 Free PMC article. No abstract available.

Abstract

Importance: Disparities in outcomes exist between Black and White patients with acute myeloid leukemia (AML), with Black patients experiencing poorer prognosis compared with their White counterparts.

Objective: To assess whether varying intensity of induction therapy to treat pediatric AML is associated with reduced disparities in treatment outcome by race.

Design, setting, and participants: A comparative effectiveness analysis was conducted of 86 Black and 359 White patients with newly diagnosed AML who were enrolled in the AML02 trial from 2002 to 2008 or the AML08 trial from 2008 to 2017. Statistical analysis was conducted from July 2023 through January 2024.

Interventions: Patients in AML02 were randomly assigned to receive standard low-dose cytarabine-based induction therapy or augmented high-dose cytarabine-based induction therapy, whereas patients in AML08 received high-dose cytarabine-based therapy.

Main outcomes and measures: Cytarabine pharmacogenomic 10-single-nucleotide variant (ACS10) scores were evaluated for association with outcome according to race and treatment arm.

Results: This analysis included 86 Black patients (mean [SD] age, 8.8 [6.5] years; 54 boys [62.8%]; mean [SD] leukocyte count, 52 600 [74 000] cells/µL) and 359 White patients (mean [SD] age, 9.1 [6.2] years; 189 boys [52.6%]; mean [SD] leukocyte count, 54 500 [91 800] cells/µL); 70 individuals with other or unknown racial and ethnic backgrounds were not included. Among all patients without core binding factor AML who received standard induction therapy, Black patients had significantly worse outcomes compared with White patients (5-year event-free survival rate, 25% [95% CI, 9%-67%] compared with 56% [95% CI, 46%-70%]; P = .03). By contrast, among all patients who received augmented induction therapy, there were no differences in outcome according to race (5-year event-free survival rate, Black patients, 50% [95% CI, 38%-67%]; White patients, 48% [95% CI, 42%-55%]; P = .78). Among patients who received standard induction therapy, those with low ACS10 scores had a significantly worse 5-year event-free survival rate compared with those with high scores (42.4% [95% CI, 25.6%-59.3%] and 70.0% [95% CI, 56.6%-83.1%]; P = .004); however, among patients who received augmented induction therapy, there were no differences in 5-year event-free survival rates according to ACS10 score (low score, 60.6% [95% CI, 50.9%-70.2%] and high score, 54.8% [95% CI, 47.1%-62.5%]; P = .43).

Conclusions and relevance: In this comparative effectiveness study of pediatric patients with AML treated in 2 consecutive clinical trials, Black patients had worse outcomes compared with White patients after treatment with standard induction therapy, but this disparity was eliminated by treatment with augmented induction therapy. When accounting for ACS10 scores, no outcome disparities were seen between Black and White patients. Our results suggest that using pharmacogenomics parameters to tailor induction regimens for both Black and White patients may narrow the racial disparity gap in patients with AML.

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Conflict of interest statement

Conflict of Interest Disclosures: Drs Lamba, Cao, and Pounds reported a having patent for Pharmacogenomics Score to Make Decisions on Therapy Augmentation in AML pending 18/683,969. Dr Inaba reported receiving personal fees from Servier, Jazz Pharmaceutical, and Amgen outside the submitted work. Dr Pui reported receiving personal fees from Novartis outside the submitted work. Dr Pounds reported receiving grants from Gateway for Cancer Research and the American Cancer Society outside the submitted work and having a patent for Leukemia Diagnostic Based on Gene Expression pending, a patent for Methods for Predicting AML Outcome pending, and a patent for AML Risk Stratification Using OS iScore pending. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Outcome According to Race
Figure 2.
Figure 2.. Event-Free Survival According to Race and Treatment for Patients Without Core Binding Factor Leukemia
Figure 3.
Figure 3.. Event-Free Survival According to Race and Cytarabine Pharmacogenomic 10–Single-Nucleotide Variant (ACS10) Score for Patients Treated With Augmented Induction Therapy
See this image and copyright information in PMC

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