# Effect of HLA restriction on racial and ethnic disparities in access to immune therapies for advanced synovial sarcoma

## TL;DR

This paper examines how HLA restrictions in immune therapies for synovial sarcoma may lead to racial and ethnic disparities in treatment access.

## Contribution

The study quantifies racial and ethnic differences in eligibility for HLA-restricted immune therapies in synovial sarcoma patients.

## Key findings

- European/European descent patients have the highest estimated eligibility (25%-39%) for HLA-restricted therapies.
- Asian/Pacific Islander patients have the lowest estimated eligibility (11%-17%) for these therapies.
- HLA-independent solutions are needed to reduce disparities in treatment access.

## Abstract

Synovial sarcoma (SS) is aggressive with poor outcomes. Cellular therapies are now FDA-approved for advanced disease, but are restricted to certain HLA-A*02 alleles. We estimate eligibility for cellular therapies by race and ethnicity.

Demographic and clinical features of SS cases from 2001 to 2020 were obtained from the United States Cancer Statistics (USCS; NPCR-SEER). Survival analyses were performed overall and by race/ethnicity. The proportion eligible for cellular therapy was estimated by race/ethnicity using previously published data on HLA-A*02 status and MAGE-A4 positivity.

From 2001 to 2020, 10 605 patients (48% female, 64% Non-Hispanic White, 17% Hispanic) with SS were identified. The incidence rate was 1.5-1.8/million/person-years and was stable over time, corresponding to an average of 530 new cases annually. The most common primary site was the extremity (n = 5877; 58%), and most patients presented with localized disease (n = 5753; 54%). The 5-year cause-specific survival was 60% across all races/ethnicities and 79% for localized, 57% for regional, and 12% for distant disease. Differences by race and ethnicity were found in the proportions of patients expected to be eligible for HLA-restricted cellular therapies targeting MAGE-A4. People of European/European descent had the highest estimated proportion (25%-39%), and people of Asian/Pacific Islander descent had the lowest (11%-17%).

Engineered T-cells targeting MAGE-A4 have shown encouraging safety and efficacy in advanced SS; however, eligibility restrictions will lead to racial and ethnic disparities. HLA-independent solutions must be developed to counter disparities and ensure all patients have access.