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211 Racial, Ethnic, and Socioeconomic Factors Result in Disparities in Outcome Among Children with Acute Lymphoblastic Leukemia Not Fully Attenuated By Disease Prognosticators: A Children’s Oncology Group (COG) StudyClinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 612. Acute Lymphoblastic Leukemias: Clinical and Epidemiological: Clinical, genetic and societal risk factors impacting ALL outcomes
Hematology Disease Topics & Pathways:
Clinical Research, Health Outcomes Research, Health Disparities Research, Clinically Relevant, Pediatric, Study Population, Clinical Practice (e.g. Guidelines, Health Outcomes and Services, and Survivorship, Value; etc.)
Saturday, December 11, 2021: 2:00 PM

Sumit Gupta, MD1,2,3, David T. Teachey, MD4, Meenakshi Devidas, PhD5*, Yunfeng Dai, PhD6*, Richard Aplenc, MD, PhD7, Lena E. Winestone, MD8, Kira O Bona, MD, MPH9,10,11, Karen R Rabin, MD, PhD12,13, Patrick A Zweidler-McKay, MD, PhD14, Kelly W Maloney, MD15, Leonard A. Mattano, MD16, Eric C Larsen, MD17*, Anne L Angiolillo, MD18*, Reuven J Schore, MD19, Michael J. Burke, MD20, Wanda L Salzer, MD21, Stuart S. Winter, MD22, Kimberly P. Dunsmore, MD23,24,25*, Naomi J Winick, MD26, William L. Carroll, MD27, Stephen P Hunger28* and Mignon L. Loh, MD29

1Institute for Health Policy, Evaluation and Management, University of Toronto, Toronto, ON, Canada
2Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada
3Faculty of Medicine, University of Toronto, Toronto, ON, Canada
4Department of Pediatrics and the Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Rutledge, PA
5Global Pediatric Medicine, St Jude Children's Research Hospital, Memphis, TN
6Department of Biostatistics, University of Florida, Gainesville, FL
7Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA
8Children's Hospital of Philadelphia, Philadelphia, PA
9Department of Pediatrics, Harvard Medical School, Boston, MA
10Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA
11Pediatric Hematology/Oncology, Children's Hospital Boston, Boston, MA
12Baylor College of Medicine TX Children's Cancer Center, Houston, TX
13Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, TX
14ImmunoGen, Waltham, MA
15Department of Pediatrics, Division of Pediatric Hematology/Oncology/BMT, Children’s Hospital Colorado and University of Colorado School of Medicine, Aurora, CO
16HARP Pharma Consulting, Mystic, CT
17Department of Pediatrics, Maine Children's Cancer Program, Scarborough, ME
18Children’s National Health System/George Washington University SMHS, Washington, DC
19Children’s National Hospital/George Washington University SMHS, Washington, DC
20Department of Pediatrics, The Medical College of Wisconsin Inc., Milwaukee, WI
21U.S. Army Medical Research and Materiel Command, Olney, MD
22Children's Minnesota Research Institute and Cancer and Blood Disorders Program, Minneapolis, MN
23Department of Pediatrics, Carilion Clinic Children's Hospital, Roanoke, VA
24Virginia Tech Carilion School of Medicine, Roanoke, VA
25Division of Oncology, University of Virginia Children’s Hospital, Charlottesville, VA
26Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX
27Division of Pediatric Hematology and Oncology, Stephen D. Hassenfeld Children's Center for Cancer and Blood Disorders, Perlmutter Cancer Center at NYU Langone Health, New York University, New York, NY
28Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
29Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of California Benioff Children’s Hospital, San Francisco, CA

Introduction: Health disparities are major issue for racial, ethnic, and socioeconomically disadvantaged groups. Though outcomes in childhood acute lymphoblastic leukemia (ALL) have steadily improved, identifying persistent disparities is critical. Prior studies evaluating ALL outcomes by race or ethnicity have noted narrowing disparities or that residual disparities are secondary to differences in leukemia biology or socioeconomic status (SES). We aimed to identify persistent inequities by race/ethnicity and SES in childhood ALL in the largest cohort ever assembled for this purpose.

Methods: We identified a cohort of newly-diagnosed patients with ALL, age 0-30.99 years who were enrolled on COG trials between 2004-2019. Race/ethnicity was categorized as non-Hispanic white vs. Hispanic vs. non-Hispanic Black vs. non-Hispanic Asian vs. Non-Hispanic other. SES was proxied by insurance status: United States (US) Medicaid (public health insurance for low-income individuals) vs. US other (predominantly private insurance) vs. non-US patients (mainly jurisdictions with universal health insurance). Event-free and overall survival (EFS, OS) were compared across race/ethnicity and SES. The relative contribution of disease prognosticators (age, sex, white blood cell count, lineage, central nervous system status, cytogenetics, end Induction minimal residual disease) was examined with Cox proportional hazard multivariable models of different combinations of the three constructs of interest (race/ethnicity, SES, disease prognosticators) and examining hazard ratio (HR) attenuation between models.

Results: The study cohort included 24,979 children, adolescents, and young adults with ALL. Non-Hispanic White patients were 13,872 (65.6%) of the cohort, followed by 4,354 (20.6%) Hispanic patients and 1,517 (7.2%) non-Hispanic Black patients. Those insured with US Medicaid were 6,944 (27.8%). Five-year EFS (Table 1) was 87.4%±0.3% among non-Hispanic White patients vs. 82.8%±0.6% [HR 1.37, 95th confidence interval (95CI) 1.26-1.49; p<0.0001] among Hispanic patients and 81.9%±1.2% (HR 1.45, 95CI 1.28-1.56; p<0.0001) among non-Hispanic Black patients. Outcomes for non-Hispanic Asian patients were similar to those of non-Hispanic White patients. US patients on Medicaid had inferior 5-year EFS as compared to other US patients (83.2%±0.5% vs. 86.3%±0.3%, HR 1.21, 95CI 1.12-1.30; p<0.0001) while non-US patients had the best outcomes (5-year EFS 89.0%±0.7%, HR 0.78, 95CI 0.71-0.88; p<0.0001). There was substantial imbalance in traditional disease prognosticators (e.g. T-cell lineage) across both race/ethnicity and SES, and of race/ethnicity by SES. For example, T-lineage ALL accounted for 17.6%, 9.4%, and 6.6% of Non-Hispanic Black, Non-Hispanic White, and Hispanic patients respectively (p<0.0001).

Table 2 shows the multivariable models and illustrates different patterns of HR adjustment among specific racial/ethnic and SES groups. Inferior EFS among Hispanic patients was substantially attenuated by the addition of disease prognosticators (HR decreased from 1.37 to 1.17) and further (but not fully) attenuated by the subsequent addition of SES (HR 1.11). In contrast, the increased risk among non-Hispanic Black children was minimally attenuated by both the addition of disease prognosticators and subsequent addition of SES (HR 1.45 to 1.38 to 1.32). Similarly, while the superior EFS of non-US insured patients was substantially attenuated by the addition of race/ethnicity and disease prognosticators (HR 0.79 to 0.94), increased risk among US Medicaid patients was minimally attenuated by the addition of race/ethnicity or disease prognosticators (HR 1.21 to 1.16). OS disparities followed similar patterns but were consistently worse than in EFS, particularly among patients grouped as non-Hispanic other.

Conclusions: Substantial disparities in survival outcomes persist by race/ethnicity and SES in the modern era. Our findings suggest that reasons for these disparities vary between specific disadvantaged groups. Additional work is required to identify specific drivers of survival disparities that may be mitigated by targeted interventions.

Disclosures: Gupta: Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Teachey: NeoImmune Tech: Research Funding; Sobi: Consultancy; BEAM Therapeutics: Consultancy, Research Funding; Janssen: Consultancy. Zweidler-McKay: ImmunoGen: Current Employment. Loh: MediSix therapeutics: Membership on an entity's Board of Directors or advisory committees.

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