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HLA 限制对晚期滑膜肉瘤免疫治疗可及性中种族和民族差异的影响

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

PubMed 2025/07/04(内容时间) Oncologist Q2 · IF 4.7(JCR 2025)

研究概要

靶向MAGE-A4的工程化T细胞在晚期SS中已显示出令人鼓舞的安全性和疗效;然而,资格限制将导致种族和民族差异。必须开发不依赖HLA的解决方案,以应对这些差异并确保所有患者都能获得治疗。

研究思路结论见上方概要

滑膜肉瘤(SS)具有侵袭性,预后较差。细胞疗法现已获FDA批准用于晚期疾病,但仅限于某些HLA-A*02等位基因。我们按种族和族裔估计了细胞疗法的适用资格。

2001年至2020年SS病例的人口学和临床特征取自美国癌症统计(USCS;NPCR-SEER)。总体及按种族/族裔进行了生存分析。根据先前发表的关于HLA-A*02状态和MAGE-A4阳性的数据,按种族/族裔估算了符合细胞治疗条件的比例。

2001年至2020年,共识别出10 605例SS患者(48%为女性,64%为非西班牙裔白人,17%为西班牙裔)。发病率为1.5-1.8/百万/人年,且随时间保持稳定,相当于每年平均530例新发病例。最常见的原发部位是肢体(n = 5877;58%),大多数患者表现为局限性疾病(n = 5753;54%)。所有种族/族裔的5年病因特异性生存率为60%,局限性疾病为79%,区域性疾病为57%,远处转移性疾病为12%。在预计符合针对MAGE-A4的HLA限制性细胞治疗条件的患者比例方面,发现了种族和族裔差异。欧洲/欧洲血统人群的估计比例最高(25%-39%),亚洲/太平洋岛民血统人群最低(11%-17%)。

展开英文摘要原文

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.

论文信息

作者
Venkataraman V、Abrams HR、Shulman DS、Loggers ET、Pollack SM、Paulson KG、Wagner MJ
单位
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, United States.United States
期刊
The oncologist2025 Jul 4
原文标识
PubMed 40554677 · DOI 10.1093/oncolo/oyaf193