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2797 Examining Disparities By Race, Ethnicity, and Socioeconomic Factors in Children and Young Adults with Relapsed Acute Lymphoblastic Leukemia: A Report from the Children’s Oncology Group

Program: Oral and Poster Abstracts
Session: 612. Acute Lymphoblastic Leukemias: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research, Lymphoid Leukemias, ALL, Clinical Research, Health outcomes research, Diversity, Equity, and Inclusion (DEI), Pediatric, Diseases, Lymphoid Malignancies, Young adult , Study Population, Human, Measurable Residual Disease
Sunday, December 8, 2024, 6:00 PM-8:00 PM

John A Ligon, MD1*, Deepa Bhojwani, MD2,3, Alice Dang4*, Lingyun Ji, PhD5*, Susan R Rheingold, MD6,7, Xinxin Xu, MS4*, Meenakshi Devidas, PhD, MBA8, John A. Kairalla, PhD9, Mary Shago, PhD10*, Nyla A. Heerema, PhD11*, Andrew J. Carroll, PhD12, Michael J. Borowitz, MD, PhD13, Brent L. Wood, MD, PhD3,14, Naomi J. Winick, MD15, William L. Carroll, MD16, Stephen P. Hunger, MD17, Elizabeth A. Raetz, MD18, Mignon L. Loh, MD, PhD19,20,21, Sumit Gupta, MD, PhD22 and Lena E Winestone, MD23

1University of Florida, Gainesville, FL
2Hematology/Oncology, Children's Hospital of Los Angeles, Los Angeles, CA
3Keck School of Medicine of University of Southern California, Los Angeles, CA
4Children's Oncology Group, Monrovia, CA
5Department of Population and Public Health Sciences, University of Southern California,, Los Angeles, CA
6Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA
7Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
8St Jude Children's Research Hospital, Memphis, TN
9University of Florida - Children's Oncology Group, Gainesville, FL
10The Hospital for Sick Children, Toronto, ON, CAN
11Ohio State University, Columbus, OH
12Department of Genetics, University of Alabama at Birmingham, Birmingham, AL
13Johns Hopkins University School of Medicine, Baltimore, MD
14Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA
15Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX
16Perlmutter Cancer Center, Department of Pediatrics and Pathology, NYU Grossman School of Medicine, New York, NY
17Division of Oncology, Childrens Hospital of Philadelphia, Philadelphia
18Department of Pediatrics, NYU Langone Health, New York, NY
19Ben Towne Center for Childhood Cancer Research, Seattle Children’s Hospital, Fred Hutch Cancer Center, University of Washington, Seattle, WA
20Department of Pediatrics, Seattle Children’s Hospital, University of Washington, Seattle, WA
21Ben Towne Center for Childhood Cancer Research, Seattle Children’s Hospital, Seattle, WA
22The Hospital For Sick Children, Toronto, ON, Canada
23Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA

Introduction: Pediatric Hispanic and non-Hispanic (NH) Black patients with newly diagnosed acute lymphoblastic leukemia (ALL) experience worse overall survival (OS) compared to NH White patients (Gupta, Lancet Haematol 2023). We hypothesized that differential outcomes by race and ethnicity (R/E) following relapse may contribute to these disparities.

Methods: We examined children and young adults with ALL enrolled on 12 frontline Children’s Oncology Group (COG) trials from 1996-2014 who subsequently relapsed. We assessed association of R/E with relapse survival predictors including time-to-relapse, relapse site, ALL risk group, and cytogenetics. We examined association of R/E with post-relapse 5-year OS and assessed the effect of disease characteristics and socioeconomic status. Socioeconomic status was evaluated using US ZIP code-based median household yearly income from the 2020 Census and US insurance status. Analyses of OS used univariate (crude) and multivariable (adjusted) Cox regression models.

Results: Among 16,115 patients with ALL treated on frontline COG trials, 2,053 (1,147 NH White, 492 Hispanic, 145 NH Black, 65 NH Asian, 184 other/unknown) relapsed and formed our primary cohort.

For B-ALL, post-relapse OS differed by R/E (p=0.002), and specifically, Hispanic patients had worse survival (46.2±2.4%, crude hazard ratio [cHR] 1.39, 95% confidence interval [CI] 1.19-1.63) compared to NH White patients (55.7±1.7%). Disease-related prognosticators, including time-to relapse (p=0.0002), white blood cell count at initial diagnosis (p=0.03), and presence of central nervous system disease at initial diagnosis (p=0.03), varied by R/E. The overall association of OS with R/E was substantially attenuated when adjusted for disease-related prognosticators and ZIP-based income (p=0.53). However, Hispanic ethnicity still associated with worse OS but by a lower magnitude (adjusted HR [aHR] 1.19, 95% CI 1.01-1.41).

Post-relapse OS in B-ALL also differed based on ZIP-based income on univariate (p=0.008) but not multivariable analysis. Focusing on the highest and lowest ZIP-based income, patients with ZIP-based income >$85,000 had better OS (56.4±2.9%) compared to those with <$50,000 (48.4±2.7%, aHR 0.77, 95% CI 0.61-0.96). NH Black patients most commonly had based income <$50,000 (46.8%), followed by Hispanic (30.6%), NH White (15.8%), and NH Asian (6.3%) patients. US insurance status also differed based on R/E (univariate p<0.0001), with NH Black patients most commonly being Medicaid insured (42.0%), followed by Hispanic (41.1%), NH White (18.3%), and NH Asian (18.0%) patients. OS was not associated with US insurance status.

For T-ALL, neither R/E nor socioeconomic status were associated with OS. For infant ALL, R/E was associated with OS on multivariable analysis (p=0.03).

Conclusions: In this large retrospective cohort of patients with relapsed ALL, we found that although R/E were associated with post relapse-OS, multivariable analyses suggest that inferior post-relapse outcomes among Hispanic and NH Black patients are in large part driven by a higher prevalence of adverse disease-related risk factors present at the time of relapse. The persistent disparity observed in Hispanic patients may be related to unmeasured underlying disease biology (such as the higher prevalence CRLF2-rearranged/Philadelphia chromosome-like B-ALL in Hispanic patients). Differing toxicities, supportive care, and adherence to treatment in the frontline setting for R/E minorities may also contribute to the differences in time-to-relapse. Our findings suggest that while post-relapse interventions are needed, the greatest impact in decreasing R/E-based ALL outcome disparities will come through identifying and targeting mechanisms in the frontline treatment setting that contribute to increased high-risk relapse among Hispanic and NH Black patients.

Disclosures: Ligon: Guidepoint Global: Consultancy, Honoraria; Capvision: Consultancy, Honoraria; Market Plus: Consultancy, Honoraria; Amgen: Research Funding. Ji: Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Rheingold: Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Wood: Amgen: Consultancy; Cellnomics LLC: Current equity holder in private company. Carroll: Merck: Consultancy. Hunger: Jazz Pharmaceuticals: Honoraria; Servier US: Honoraria; Amgen: Current equity holder in publicly-traded company, Honoraria; Novartis: Consultancy. Gupta: Amgen: Other: Educational session.

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*signifies non-member of ASH