CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
结外弥漫大 B 细胞淋巴瘤对抗 CD19-CAR-T 细胞的缓解率：一项真实世界回顾性多中心研究
英文原题：Response rates of extra-nodal diffuse large B cell lymphoma to anti-CD19-CAR T cells: A real word retrospective multicenter study.
查看英文原题
Response rates of extra-nodal diffuse large B cell lymphoma to anti-CD19-CAR T cells: A real word retrospective multicenter study.
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中文摘要
CAR-T 细胞广泛用于治疗复发/难治性弥漫大B细胞淋巴瘤（DLBCL），但其用于结外（EN）淋巴瘤患者的数据有限。我们纳入126例连续DLBCL患者，均接受了商业化CAR-T 细胞治疗（tisagenlecleucel 100例，占79.4%；axicabtagene ciloleucel 26例，占20.6%）。在淋巴细胞清除时，72/126例（57%）患者有结外疾病，42/126例（33%）仅有淋巴结疾病（ND），12/126例（10%）PET-CT未检出疾病。EN患者与ND患者CAR-T 相关毒性和中位无进展生存期（PFS）均无显著差异（10.76个月［95% CI 7.8–13.6］比14.1个月［95% CI 10–18.1］，p=0.126）。
类似地，两组中位总生存期（OS）也无显著差异（15.36个月［95% CI 12.5–18.2］比18.4个月［95% CI 14.8–22.1］，p=0.100）。根据结外受累部位数量进行亚组分析发现，结外受累部位<3处的患者，中位PFS和OS显著高于结外受累部位≥3处的患者；相应PFS为12.3个月（95% CI 9–15.5）比4.28个月（95% CI 0.6–7.9），p=0.010；OS为16.5个月（95% CI 13.4–19.6）比8.7个月（95% CI 4.6–12.8），p=0.05。多变量Cox回归分析中，淋巴细胞清除时结外病灶数量增加及LDH升高会降低PFS（p分别为0.021和<0.001）；性别、CAR-T 产品类型、年龄和体能状态均不能预测PFS或OS。
值得注意的是，淋巴细胞清除时胃肠道（n=9）、泌尿道（n=9）或咽部（n=3）受累的所有患者均发生疾病进展或早期复发。总之，淋巴细胞清除时结外受累部位≥3处的患者，临床结局显著差于结外受累部位<3处者；特定部位结外病变患者可能预后极差。
展开英文摘要原文
Chimeric antigen receptor T-cells (CAR-T) are widely used for the treatment of relapsed/refractory diffuse large B cell lymphoma (DLBCL). The data for CAR-T cell therapy in patients with extra-nodal (EN) lymphoma is restricted.
We included 126 consecutive patients with DLBCL treated with commercially available CAR-T cells (tisagenlecleucel, n = 100, 79. 4% and axicabtagene ciloleucel, n = 26, 20. 6%). At lymphodepletion, 72 of 126 (57%) patients had EN disease, 42 of 126 (33%) patients had nodal disease (ND)-only and 12 of 126 (10%) showed no disease assessed by PET-CT. There were no significant differences in CAR-T related toxicities and in the median Progression free survival (PFS) between EN patients and ND (10. 76 [95% CI: 7. 8-13. 6] vs. 14. 1 [95% CI: 10-18. 1] months, p = . 126). Similarly, median overall survival (OS) was not significantly different (15. 36 [95% CI 12. 5-18. 2] vs. 18. 4 [95% CI 14. 8-22. 1] months, p = . 100).
Subgroup analysis according to the number of EN involved sites showed that median PFS and OS were significantly higher in patients with <3 EN sites (12. 3 months [95% CI 9-15. 5] vs. 4. 28 months [95% CI 0. 6-7. 9], p = . 010) compared to patients with >2 EN sites, respectively (16. 5 months [95% CI 13. 4-19. 6] vs. 8. 7 months [95% CI 4. 6-12. 8], p = . 05).
In multivariate cox regression analysis, increased number sites of EN disease and high lactate dehydrogenase (LDH) at lymphodepletion negatively impacted PFS (p = . 021 and <. 001, respectively), while sex, type of product administered, age and performance status did not predict PFS and OS. Of note, all the patients with involvement of gastrointestinal tract (n = 9), urinary tract (n = 9), or pharynx (n = 3) at lymphodepletion, progressed or had an early relapse.
In conclusions, patients with >2 EN sites at lymphodepletion have significantly worse clinical outcomes compared to patients with <3 EN sites. Patients with specific sites of EN disease may demonstrate grim prognosis.
论文信息
- 作者
- Beyar Katz O、Perry C、Grisariu-Greenzaid S、Yehudai-Ofir D、Luttwak E、Avni B、Zuckerman T、Sdayoor I
- 第一作者单位
- Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel.Israel
- 通讯作者单位
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.Israel
- 文献类型
- 多中心研究
- 期刊
- European journal of haematology2023 Jul
- 原文标识
- PubMed 36964939 · DOI 10.1111/ejh.13968