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2430 Survival Disparities By Frontline Clinical Trial Enrollment Status for Treatment of Pediatric Acute Myeloid Leukemia

Program: Oral and Poster Abstracts
Session: 906. Outcomes Research – Myeloid Malignancies: Poster I
Hematology Disease Topics & Pathways:
Acute Myeloid Malignancies, Research, AML, epidemiology, Clinical Research, health outcomes research, pediatric, Diversity, Equity, and Inclusion (DEI) , health disparities research, Diseases, real-world evidence, Myeloid Malignancies, Human, Study Population
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Daniel J. Zheng, MD1,2, Elsa van der Mei, MPH1,3*, Yimei Li, PhD1,4*, Yuan-Shung V. Huang, MS5*, Catherine Aftandilian, MD6, Kira Bona, MD, MPH7, Emi Caywood, MD8,9, Anderson B. Collier, MD10*, M. Monica Gramatges, MD, PhD11,12, Mallorie M. Heneghan, MD13, Meret Henry, MD14, Craig Lotterman, MD15*, Kelly Maloney, MD16,17*, Tamara P. Miller, MD18,19, Arunkumar Modi, MBBS20, Rajen Mody, MD, MS21*, Elaine Morgan, MD22, Naomi J. Winick, MD23, Jennifer J. Wilkes, MD, MSCE24,25, Victor Wong, MD26*, Haley Newman, MD1, Regina M. Myers, MD1, Caitlin W. Elgarten, MD1, Alix E. Seif, MD, MPH1, Brian T. Fisher, DO, MPH, MSCE3,27*, Richard Aplenc, MD, PhD1,28 and Kelly D. Getz, PhD4,29*

1Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA
2National Clinician Scholars Program, University of Pennsylvania, Philadelphia, PA
3Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
4Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
5Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA
6Department of Pediatrics, Division of Hematology, Oncology and Stem Cell Transplant, Stanford University, Palo Alto, CA
7Division of Pediatric Hematology/Oncology, Boston Children’s Hospital, Boston, MA
8Department of Pediatrics, Thomas Jefferson University, Philadelphia, PA
9Nemours Children's Health, Wilmington, DE
10University of Mississippi, Jackson, MS
11Baylor College of Medicine, Houston, TX
12Pediatric Hematology-Oncology, Texas Children's Hospital, Houston, TX
13Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Utah, Salt Lake City, UT
14Children's Hospital of Michigan, Detroit, MI
15Ochsner Medical Center for Children, New Orleans, LA
16Department of Pediatrics, Children's Hospital Colorado, Aurora, CO
17University of Colorado School of Medicine, Aurora, CO
18Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA
19Department of Pediatrics, Emory University School of Medicine, Decatur, GA
20Division of Pediatric Hematology Oncology, Arkansas Children's Hospital, Little Rock, AR
21University of Michigan, Ann Arbor, MI
22Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL
23Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX
24Department of Pediatrics, University of Washington School of Medicine, Seattle, WA
25Division of Hematology/Oncology, Seattle Children's Hospital, Seattle, WA
26Division of Pediatric Hematology Oncology, Rady Children's Hospital of San Diego, San Diego, CA
27Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, PA
28Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
29Division of Oncology, University of Pennsylvania, Philadelphia, PA

Introduction: Studies have suggested superior outcomes for patients enrolled on clinical trials for their cancer treatment. While sociodemographic disparities in trial enrollment are well established in adults, the literature in children is mixed and limited. A deeper understanding of disparities in pediatric clinical trial enrollment and potential survival differences is critical to ensure the generalizability of trial results and equitable outcomes. In a cohort of children with AML, we sought to examine (1) differences in sociodemographic and clinical characteristics by trial enrollment status, (2) the impact of trial enrollment on survival, and (3) the potential drivers of survival differences.

Methods: A retrospective cohort including all pediatric (age <19 years) patients with AML treated at 10 institutions in the United States from 2011-2018 was established and is being actively expanded to include diagnoses through 2023. Chart abstraction by trained study personnel collected detailed demographic and clinical information. Resource utilization data from the Pediatric Health Information System was merged to ascertain patient acuity. Higher acuity was defined as requiring ICU-level resources for 2 or more organ systems within 72 hours of diagnosis. Only patients who had a frontline therapeutic trial option available at their treating institution were included. This was operationalized as a center-level restriction to patients initiating therapy while any frontline trial was enrolling at the center. We additionally included only patients with complete data for all covariates in this analysis.

Statistical Analysis: Demographic and clinical characteristics by trial enrollment status were compared using t-test or Fisher’s exact test as appropriate. Cox proportional hazards regression estimated hazard ratios (HR) with a doubly robust estimator (adjusted models only) of 4-year OS and EFS by trial enrollment status. A stepwise propensity score (PS) approach assessed the impact of potential drivers of the associations between trial enrollment and overall survival (OS) and event-free survival (EFS). PS were computed by logistic regression and generated stabilized inverse probability weights used for adjustment. First, a Base PS model including a predefined set of potential confounders (age, sex, weight category, preferred language, risk classification, mean annual hospital AML volume) was created. Additional variables of interest were then sequentially added to the PS. The change in adjusted HR relative to the unadjusted comparison was used to quantify the proportion of the association explained at each step.

Results: 342 pediatric patients diagnosed with AML with representation from three distinct frontline clinical trials (AAML1031, AML08, and AML16) were included. Patients who were Black (11% vs. 24%), Hispanic (24% vs. 28%), publicly insured (44% vs. 55%), higher acuity (3% vs. 8%), and high-risk classification (29% vs. 34%) were underrepresented in the trial enrollment group compared to non-trial enrolled (Table 1). In unadjusted analyses, trial enrollment was significantly associated with superior OS (HR=0.69, 95% CI 0.47-0.99, p=0.04); there was no significant difference in EFS (HR=0.95, 95% CI 0.69-1.31, p=0.75). Adjustment for the Base PS accounted for 23% of the observed association between trial enrollment and OS (Figure 1). Acuity explained an additional 7% of the association. Inclusion of race/ethnicity and insurance did not result in further adjustment. In fully adjusted analysis, the association was substantially attenuated (HR=0.93, 95% CI 0.59-1.46, p=0.76).

Conclusions: Significant sociodemographic and clinical differences exist in frontline trial enrollment for pediatric AML, which may contribute to worse overall survival outcomes for patients not enrolled on trials. Acuity at diagnosis may be a potential modifiable driver of survival differences. These findings support the need to evaluate enrollment patterns across pediatric clinical trials, including how enrollment disparities impact generalizability of clinical trial results, as well as a critical need for interventions designed to improve equity in healthcare access.

Disclosures: Elgarten: Allovir: Other: one time advisory committee. Fisher: Merck: Research Funding; Pfizer: Research Funding; Astellas: Other: Membership on Data safety monitoring board; Allovir: Research Funding.

*signifies non-member of ASH