Role of race and ethnicity in survival among children/young adults with relapsed ALL: a Children's Oncology Group report Open Access

• The association of race and ethnicity with worse post relapse B-ALL survival is largely accounted for by disease and socioeconomic factors.

• Hispanic patients had higher mortality following B-ALL relapse even after accounting for known prognostic factors such as early relapse.

Pediatric Hispanic and Black patients with newly diagnosed B-acute lymphoblastic leukemia (B-ALL) experience worse overall survival (OS). We hypothesized that differential outcomes by race and ethnicity following relapse may contribute to disparities. We examined 2,053 patients with ALL enrolled on frontline Children's Oncology Group trials from 1996-2014 who relapsed. We assessed association of race and ethnicity, disease characteristics, and socioeconomic status with relapse survival predictors and post-relapse OS. For non-infant B-ALL, post-relapse OS (p=0.002) and disease-related prognosticators such as time-to-relapse (p=0.0002) differed by race and ethnicity. After adjusting for disease and patient characteristics, the OS association with overall race and ethnicity was attenuated, and lost statistical significance; Hispanic ethnicity specifically remained associated with worse OS (hazard ratio, HR=1.19, 95% confidence interval, CI 1.01-1.41). Patients from highest annual median household income ZIP codes (>$85,000, ~highest quartile of patients) had better 5-year OS compared to those from the lowest (<$50,000, HR=0.79, 95%CI 0.63-0.99). Non-Hispanic Black and Hispanic patients more commonly lived in lower income ZIP codes. For T-ALL, race, ethnicity and socioeconomic status were not associated with OS. Worse post-relapse outcomes among racial and ethnic minority patients are largely driven by prevalence of adverse disease-related factors at time of relapse, with a persistent disparity observed in Hispanic patients. The greatest impact in decreasing racial and ethnic B-ALL outcome disparities may come through targeting frontline treatment interventions to address increased relapse among Black and Hispanic patients, as well as developing and enabling equitable access to effective relapse treatments such as novel immunotherapies. (CCG 1991, POG 9404, POG 9407, POG 9904, POG 9905, POG 9906, COG AALL0232, COG AALL0331, COG AALL0434, COG AALL0631, COG AALL07P4, COG AALL08P1)