Area deprivation index independently predicts outcomes in IPSS-R higher-risk myelodysplastic syndromes at a major cancer center

Abstract

Abstract Introduction: The Area Deprivation Index (ADI), which measures neighborhood disadvantage using 17 socioeconomic factors, is a well-validated tool for assessing health equity (Powell et al., Forefront, 2023). ADI is an independent prognostic factor in solid tumors, such as breast, ovarian, and prostate cancers, and acute leukemias. However, its impact on patients with myelodysplastic syndromes (MDS) is unclear. We evaluated outcomes in patients with higher-risk (HR) MDS, defined by an IPSS-R score >3.5, treated at MD Anderson Cancer Center (MDACC). Methods: In this retrospective analysis, previously untreated adult patients with HR-MDS managed at MDACC from 2000 to 2023 were included. Patient and disease characteristics and addresses at the index visit to the MDACC leukemia clinic were abstracted from electronic medical records. Patient zip codes were linked to the 2020 ADI national percentile ranks from the Neighborhood Atlas. ADI percentiles were quartiled (Q) with Q1 (0-25) representing the least disadvantaged neighborhoods and Q4 (76-100) comprised of neighborhoods with the greatest deprivation. Kruskal-Wallis and Fisher's Exact Test were used to compare covariates across ADI quartiles. Stem cell transplantation (SCT) was included as a time-dependent covariate. Backward elimination was applied in multivariate analysis (MVA), retaining variables with p ≤0.1. Results: Of 2,044 patients with HR-MDS that were identified, 1,999 patient zip codes were able to be linked to ADI national percentile ranks. When stratified by ADI quartiles: Q1, 290 (15%); Q2, 582 (29%); Q3, 755 (38%); Q4, 372 (19%). The median age of the cohort was 67 years (range, 17–94). No significant differences were observed in median age, therapy-related MDS (t-MDS), absolute neutrophil count, bone marrow blasts, complex cytogenetics, or TP53 mutations (monoallelic or biallelic) across ADI quartiles. No differences were noted in first-line treatment types or clinical trial enrollment rates. However, SCT rates differed significantly across quartiles: Q1, 27%; Q2, 21%; Q3, 20%; Q4, 19% (p = 0.038). The rate of transformation to acute myeloid leukemia (AML) was in Q3 (29%, p = 0.009). In MVA, younger age (HR 0.65, 95% CI 0.49–0.86, p = 0.003), first-line clinical trial treatment (HR 0.72, 95% CI 0.59–0.88, p = 0.001), and SCT (HR 0.65, 95% CI 1.59–2.54, p < 0.001) were associated with longer overall survival (OS). Conversely, ECOG PS >2 (HR 1.37, 95% CI 1.01–1.85, p = 0.040), t-MDS (HR 1.43, 95% CI 1.17-1.74, p = 0.001), higher circulating blasts (HR 1.03, 95% CI 1.00–1.06, p = 0.029), elevated creatinine (HR 1.30, 95% CI 1.08–1.56, p = 0.005), elevated total bilirubin (HR 1.32, 95% CI 1.19–1.46, p < 0.001), very high-risk IPSS-R (HR 1.68, 95% CI 1.36–2.09, p < 0.001), monoallelic TP53 mutation (HR 2.03, 95% CI 1.61–2.57, p < 0.001), and biallelic TP53 mutations (HR 1.78, 95% CI 1.35–2.35, p < 0.001) were associated with shorter OS. Compared to Q1, ADI national quartiles Q2 (HR 1.48, 95% CI 1.07–2.05, p = 0.018), Q3 (HR 1.40, 95% CI 1.02–1.92, p = 0.035), and Q4 (, p = 0.001) were associated with increased risk of death. Beyond known MDS prognostic factors, clinical trial participation was associated with longer OS. Notably, ADI national rank was an independent prognostic factor in HR-MDS, with higher ADI quartiles (Q2–Q4) linked to significantly shorter OS. Conclusion: ADI is an independent prognostic factor in patients with HR-MDS at a large academic center. Robust resources and sustained initiatives for ensuring equitable, continuous healthcare access are critical to overcoming this disparity.