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

PURPOSE

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.

MATERIALS AND METHODS

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.

RESULTS

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%).

CONCLUSION

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.