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
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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