THE ASSOCIATION OF SOCIAL DISADVANTAGE WITH OUTCOMES IN PATIENTS WITH ADVANCED-STAGE, CLASSIC HODGKIN LYMPHOMA ENROLLED IN THE PHASE 3 INTERGROUP TRIAL S1826

J. M. Unger, H. Li, S. M. Castellino, H. Dillon, T. Hernandez, S. C. Rutherford, A. Punnett, M. LeBlanc, J. Y. Song, S. M. Smith, A. M. Evens, K. M. Kelly, J. W. Friedberg, and A. Herrera equally contributing author.

Background: The phase 3 randomized trial S1826 showed that among patients with advanced-stage classic Hodgkin lymphoma (cHL), nivolumab plus doxorubicin, vinblastine, and dacarbazine (N+AVD) resulted in longer progression-free survival (PFS) compared to brentuximab vedotin plus AVD (BV+AVD). We assessed whether the treatment benefits of N+AVD applied to potentially socioeconomically vulnerable populations.

Methods: S1826 was a multicenter trial for patients ≥ 12 years old with stage III or IV newly diagnosed cHL. The trial was stopped early at its pre-specified second interim analysis due to efficacy of the N+AVD arm (hazard ratio [HR] for progression or death, 0.48; 95% confidence interval [CI], 0.27–0.87, p = 0.001). We assessed whether there was any evidence of differential benefit of N+AVD with respect to PFS according to categories of race/ethnicity (Black race and/or Hispanic ethnicity vs. others), rural versus urban residence, area-level socioeconomic deprivation (Area Deprivation Index [ADI] above median, yes vs. no), and insurance status (Medicaid or no insurance vs. others) using interaction tests. Analyses were conducted using Cox regression adjusting for the study-specified stratification variables including age (12 –17 vs. 18–60 vs. > 60 years), the international prognostic score (IPS; 0–3 vs. 4–7), and intent to use radiation (yes vs. no). An overall Type I error rate of alpha = 0.10 was used; multiplicity was accounted for by specifying each individual test at the two-sided alpha = 0.025 level using Bonferroni. If no interaction was found, the marginal association of socioeconomic variables and PFS using multivariable Cox regression was examined.

Results: Of N = 970 eligible patients, 90% were < 60 years, and 56% were male; 11.8% were Black, 12.7% were Hispanic, and 32% had IPS 4–7. Among socioeconomic variables, the combined Black and/or Hispanic patients comprised 24.5%, 13.3% were from rural areas, 50% lived in areas above the median ADI level, and 23.2% had Medicaid or no insurance. In survival analyses, there was no statistically significant evidence that the effect of treatment on PFS differed between levels of the socioeconomic variables (Table). For instance, the PFS HR was 0.52 for Black and/or Hispanic patients and 0.41 for other patients (interaction p-value = 0.60). Across all patients, there was no statistically significant association of Black and/or Hispanic race/ethnicity (HR = 1.10, 95% CI: 0.72–1.69, p = 0.65), rural geography (HR = 1.11, 95% CI: 0.67–1.85, p = 0.67), high ADI (HR = 1.30, 95% CI: 0.89–1.88, p = 0.17), or Medicaid/no insurance (HR = 1.01, 95% CI: 0.63–1.60, p = 0.98) with PFS.

Conclusion: Among patients with advanced stage cHL enrolled on S1826, we found no evidence that the PFS benefit of N+AVD compared to BV+AVD was meaningfully attenuated by factors representing social disadvantage. This suggests widespread applicability of N+AVD for patients of different socioeconomic backgrounds. Overall survival analyses are ongoing.

Research funding declaration: National Cancer Institute of the National Institutes of Health U10CA180888, U10CA180819; in part by BMS; Emmet & Toni Stephenson Leukemia Lymphoma Society (LLS) Scholar Award; LRF Larry & Denise Mason Clinical Scholar Career Development Award; V Foundation Lloyd Family Clinical Investigator Fund; LLS Clinical Research Scholar Award.

Keywords: cancer health disparities

No potential sources of conflict of interest.