Abstract IA37: Survival by race and ethnicity in pediatric and adolescent patients with Hodgkin lymphoma: A report from the Children’s Oncology Group
Authors: Kahn Justine , Kelly Kara M. , Pei Qinglin , Bush Rizvan , Friedman Debra L. , Keller Frank G. , Bhatia Smita , Henderson Tara O. , Schwartz Cindy L. , Castellino Sharon M. 
Published: September 2020

Background: While survival in Hodgkin lymphoma (HL) is excellent, disparities by race/ethnicity have been described. Population-based and single-center studies of children and adolescents with Hodgkin lymphoma (HL) report a survival disadvantage in non-Hispanic black (NHB) and Hispanic (vs. non-Hispanic white [NHW]) patients (Grubb, Pediatr Blood Cancer 2016; Metzger, JCO 2008). These studies, though suggestive of a significant public health disparity, are often limited by lack of information about disease characteristics and therapeutic exposures. Thus, whether racial/ethnic disparities persist after adjustment for clinical and treatment-related variables remains a subject of debate. We examined event-free survival (EFS) and overall survival (OS) in NHW, NHB and Hispanic patients receiving risk-stratified, response-adapted therapy for de novo HL on contemporary Children’s Oncology Group (COG) trials.

Methods: This was a pooled analysis of individual, patient-level data from 1,605 children and adolescents (&lt;1 – 21 years) enrolled on three consecutive phase III clinical trials for treatment of intermediate, low-, and high-risk HL (AHOD0031, AHOD0431, AHOD0831). Event-free survival and OS were compared between NHW and non-white patients (NHB and Hispanic) and were estimated using the Kaplan-Meier method. Cox Proportional Hazards for survival were estimated for both de novo and relapsed HL, adjusting for age, sex, insurance, histology, Ann Arbor stage, B-symptoms, bulk disease, COG study, and radiation therapy (RT).

Results: Between 2002 and 2012, 2,155 patients enrolled on COG trials for the treatment of newly diagnosed HL; 1,605 (76%) were included in this study. Patients treated outside of the United States (N= 299), with lymphocyte predominant histology (N= 86), and who withdrew consent after one cycle (N= 37), were excluded. For the purpose of this study, analyses were restricted to patients who were NHW, NHB, and Hispanic. In total, N= 49 patients who were Asian/Pacific Islander and N= 79 patients who were other/mixed race were excluded. Sixty-seven percent of the study cohort (N= 1,083) was NHW. Among non-white patients (N= 522), 13% were NHB and 20% were Hispanic. Median age was 14.6 years (± 3.5 years). Approximately 16% of NHW patients vs. 41% and 44% of NHB and Hispanic patients had public or government insurance (P&lt; 0.01). Non-white patients were also more to come from low-income households (P &lt; 0.01). Compared with non-white patients, a higher proportion of NHW children had nodular sclerosing histology (P&lt; 0.01). A higher proportion of non-white patients presented with stage III/IV (vs. I/II, P&lt; 0.01) and bulky disease (P= 0.04); however, there was no difference in receipt of RT by race/ethnicity. At median follow-up of 6.9 years, cumulative incidence of relapse was 17% and did not significantly differ by race/ethnicity. Unadjusted 5-year EFS and OS were 83% (standard error [SE]: 1.2%) and 97% (SE: &lt;1%), respectively, and neither differed by race/ethnicity. In multivariable analyses for OS, non-white patients had 1.88-times higher hazard of death (95% confidence interval [CI]: 1.1 –3.3). Five-year post-relapse survival probabilities by race were NHW: 90%, NHB: 66%, Hispanic: 80% (P&lt; 0.01). Compared with NHW patients, Hispanic and NHB children had 2.7-fold (95% CI: 1.2 –6.2) and 3.5-fold (95% CI: 1.5 –8.2) increased hazards of post-relapse mortality, respectively.

Conclusion: In the controlled setting of COG clinical trials, treatment with dose-dense, response-adapted therapy for newly diagnosed HL eliminates racial/ethnic differences in EFS. This observation suggests that current approaches to risk stratification with response-adapted regimens are highly effective for both NHW and non-white children with HL. Though there was no difference in EFS across NHW and non-white patients in our cohort, the striking difference in the risk of all-cause mortality lends weight to the possibility that differences in cancer therapy or supportive care outside of the cooperative group setting may be driving the disparities observed at the population level. Critical areas of future study to reduce racial disparities in HL should focus on improving health equity, expanding clinical trial participation, and dentifying drivers of racial/ethnic disparities in children with relapsed disease.

Research support: This work was supported by the Children’s Oncology Group Chair Grant No. U10CA98543, the Children’s Oncology Group Statistics and Data Center Grant No. U10CA098413, the National Clinical Trials Network Operations Center Grant No. U10CA180886, and the National Clinical Trials Network Statistics and Data Center Grant No. U10CA180899. This work was also supported by the St. Baldrick’s Foundation, the Lymphoma Research Foundation, and by a KL2 Mentored Career Development Award Grant No. KL2-TR001874 from the Irving Institute for Clinical and Translational Research at Columbia University Irving Medical Center.

Citation Format: Justine Kahn, Kara M. Kelly, Qinglin Pei, Rizvan Bush, Debra L. Friedman, Frank G. Keller, Smita Bhatia, Tara O. Henderson, Cindy L. Schwartz, Sharon M. Castellino. Survival by race and ethnicity in pediatric and adolescent patients with Hodgkin lymphoma: A report from the Children’s Oncology Group [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr IA37.