Poverty and Targeted Immunotherapy: Survival in Children's Oncology Group Clinical Trials for High-Risk Neuroblastoma

Abstract

Background: Whether social determinants of health are associated with survival in the context of pediatric oncology-targeted immunotherapy trials is not known. We examined the association between poverty and event-free survival (EFS) and overall survival (OS) for children with high-risk neuroblastoma treated in targeted immunotherapy trials.

Methods: We conducted a retrospective cohort study of 371 children with high-risk neuroblastoma treated with GD2-targeted immunotherapy in the Children's Oncology Group trial ANBL0032 or ANBL0931 at a Pediatric Health Information System center from 2005 to 2014. Neighborhood poverty exposure was characterized a priori as living in a zip code with a median household income within the lowest quartile for the cohort. Household poverty exposure was characterized a priori as sole coverage by public insurance. Post hoc analyses examined the joint effect of neighborhood and household poverty using a common reference. All statistical tests were 2-sided.

Results: In multivariable Cox regressions adjusted for disease and treatment factors, household poverty-exposed children experienced statistically significantly inferior EFS (hazard ratio [HR] = 1.90, 95% confidence interval [CI] = 1.28 to 2.82, P = .001) and OS (HR = 2.79, 95% CI = 1.63 to 4.79, P < .001) compared with unexposed children. Neighborhood poverty was not independently associated with EFS or OS. In post hoc analyses exploring the joint effect of neighborhood and household poverty, children with dual-poverty exposure (neighborhood poverty and household poverty) experienced statistically significantly inferior EFS (HR = 2.21, 95% CI = 1.48 to 3.30, P < .001) and OS (HR = 3.70, 95% CI = 2.08 to 6.59, P < .001) compared with the unexposed group.

Conclusions: Poverty is independently associated with increased risk of relapse and death among neuroblastoma patients treated with targeted immunotherapy. Incorporation of social and environmental factors in future trials as health-care delivery intervention targets may increase the benefit of targeted therapies.

Figure 1.

Consort diagram of cohort creation. ASCT = autologous stem cell transplantation.

Figure 2.

Survival among children with high-risk neuroblastoma receiving targeted immunotherapy on Children’s Oncology Group (COG) protocols ANBL0032 or ANBL0931 at a Pediatric Health Information System (PHIS) center. Data are shown for Kaplan-Meier estimates of event-free survival (EFS) and overall survival (OS) for overall cohort from time of trial enrollment. Trial enrollment occurred after completion of both induction and consolidation therapy A). Two-year estimates (95% confidence interval [CI]): EFS = 67.9% (95% CI = 61.9% to 73.2%); OS = 85.5% (95% CI = 80.6% to 89.3%). B) Data for EFS and OS = stratified by neighborhood poverty group. Two-year estimates (95% CI): EFS no neighborhood poverty = 70.0% (95% CI = 63.1% to 75.8%) vs neighborhood poverty = 61.6% (95% CI = 48.5% to 72.3%), log rank test P = .15; OS no neighborhood poverty = 87.7% (95% CI = 82.2% to 91.6%) vs neighborhood poverty = 78.8% (95% CI = 66.6% to 87.0%), log rank test P = .07. C) EFS and OS stratified by household  poverty group. Two-year estimates (95% CI): EFS no household poverty = 75.7% (95% CI = 68.8% to 81.2%) vs household poverty = 50.9% (95% CI = 39.4% to 61.3%), log rank test (P < .001); OS no household poverty = 90.9% (95% CI = 85.6% to 94.3%) vs household poverty = 74.4% (95% CI = 63.4% to 82.5), log rank test P < .001.

Figure 3.

Survival by combined poverty status among children with high-risk neuroblastoma receiving targeted immunotherapy on Children’s Oncology Group (COG) protocols ANBL0032 or ANBL0931 and treated at a Pediatric Health Information System (PHIS) center. Data are shown for Kaplan-Meier estimates of (A) event-free survival (EFS) from time of trial enrollment by combined neighborhood and household poverty, 2-year estimates: no poverty = 76.5% (95% CI = 68.9% to 82.4%), single-neighborhood poverty = 70.9% (95% CI = 52.5% to 83.3%), single-household poverty = 52.1% (95% CI = 37.7% to 64.7%), dual-poverty = 54.5% (95% CI = 36.2% to 69.5%), log-rank P value = .005; and B) overall survival (OS) from time of trial enrollment by combined neighborhood and household poverty, 2-year estimates: no poverty = 90.1% (95% CI = 83.8% to 94.0%), single-neighborhood poverty = 94.3% (95% CI = 79.0% to 98.5%), single-household poverty = 81.2% (95% CI = 67.6% to 89.6%), dual poverty = 64.3% (95% CI = 45.0% to 78.3%), log rank test P less than .001. Trial enrollment occurred after completion of both induction and consolidation therapy.