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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
复发/难治性 B 细胞淋巴瘤 CD19 CAR-T 细胞治疗后免疫重建的预后意义
英文原题：Prognostic significance of immune reconstitution following CD19 CAR T-cell therapy for relapsed/refractory B-cell lymphoma.
查看英文原题
Prognostic significance of immune reconstitution following CD19 CAR T-cell therapy for relapsed/refractory B-cell lymphoma.
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中文摘要
CD19 嵌合抗原受体 (CAR) T 细胞治疗后的免疫缺陷可持续很长时间，使患者易发生感染和非复发死亡。在 B 细胞非霍奇金淋巴瘤 (B-NHL) 中，免疫重建 (IR) 的预后影响仍不明确，且迄今为止尚未进行详细的不同产品间比较。在这项回顾性观察性研究中，我们纵向描述了 105 例 B-NHL 患者的淋巴细胞亚群和免疫球蛋白水平，以评估 CD19 CAR-T 后出现的免疫恢复模式。三项关键 IR 标准定义为 CD4 + T 辅助 (T H) 细胞 > 200/ L、可检测到任何 B 细胞，以及血清免疫球蛋白 G (IgG) 水平 >4 g/L。
中位随访 24.6 个月后，38% 的患者显示 T H 细胞，11% 显示任何 B 细胞，41% 出现 IgG 恢复。出现了显著的产品特异性差异，包括 CD28z- 产品的 T H 细胞缺乏更深，而基于 41BBz 的产品 B 细胞缺乏更长。任何 IR 恢复的患者均获得了延长的无进展生存期 (PFS)（中位 20.8 个月 vs. 1.7 个月，p < 0.0001）和总生存期 (OS)（34.9 个月 vs. 4.0 个月，p < 0.0001）。尽管 90 天界标分析证实任何恢复的患者 PFS 改善（34.9 个月 vs. 8.6 个月，p = 0.005），但未观察到显著的 OS 差异。
值得注意的是，72% 的难治性疾病患者从未显示任何 IR 标准的恢复。与晚期进展/复发（第 90 天后）患者相比，早期进展患者在进展/复发时表现出减弱的 IR。
我们的结果强调了 CD19 CAR-T 后观察到的深刻免疫缺陷，并揭示了 B-NHL 中 IR 与疗效的交叉关系。重要的是，进展后IR受到显著损害，这对后续针对T细胞的疗法及治疗排序具有重大意义。
展开英文摘要原文
Immune deficits after CD19 chimeric antigen receptor (CAR) T-cell therapy can be long-lasting, predisposing patients to infections and non-relapse mortality. In B-cell non-Hodgkin lymphoma (B-NHL), the prognostic impact of immune reconstitution (IR) remains ill-defined, and detailed cross-product comparisons have not been performed to date. In this retrospective observational study, we longitudinally characterized lymphocyte subsets and immunoglobulin levels in 105 B-NHL patients to assess patterns of immune recovery arising after CD19 CAR-T. Three key IR criteria were defined as CD4 + T helper (T H ) cells > 200/ L, any detectable B cells, and serum immunoglobulin G (IgG) levels >4 g/L.
After a median follow-up of 24. 6 months, 38% of patients displayed T H cells, 11% showed any B cells, and 41% had IgG recovery. Notable product-specific differences emerged, including deeper T H cell aplasia with CD28z- versus longer B-cell aplasia with 41BBz-based products.
Patients with any IR recovery experienced extended progression-free survival (PFS) (median 20. 8 vs. 1. 7 months, p < 0. 0001) and overall survival (OS) (34. 9 vs. 4. 0 months, p < 0. 0001). While landmark analysis at 90 days confirmed improved PFS in patients with any recovery (34. 9 vs. 8. 6 months, p = 0. 005), no significant OS difference was noted.
Notably, 72% of patients with refractory disease never displayed recovery of any IR criteria. Early progressors showed diminished IR at the time of progression/relapse compared to patients with late progression/recurrence (after Day 90).
Our results highlight the profound immune deficits observed after CD19 CAR-T and shed light on the intersection of IR and efficacy in B-NHL.
Importantly, IR was impaired considerably postprogression, carrying significant implications for subsequent T-cell-engaging therapies and treatment sequencing.
论文信息
- 作者
- Stock S、Bücklein VL、Blumenberg V、Magno G、Emhardt AJ、Holzem AME、Cordas Dos Santos DM、Schmidt C
- 单位
- Department of Medicine III LMU University Hospital LMU Munich Munich Germany.Germany
- 期刊
- HemaSphere2025 Jan
- 原文标识
- PubMed 39807276 · DOI 10.1002/hem3.70062
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