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
维生素 D 不足与大 B 细胞淋巴瘤 CAR-T 细胞治疗的临床结局
英文原题：Vitamin D Insufficiency and Clinical Outcomes with Chimeric Antigen Receptor T-Cell Therapy in Large B-cell Lymphoma.
查看英文原题
Vitamin D Insufficiency and Clinical Outcomes with Chimeric Antigen Receptor T-Cell Therapy in Large B-cell Lymphoma.
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中文摘要
维生素D不足是新诊断大B细胞淋巴瘤（LBCL）不良预后的潜在可干预危险因素。然而，循环维生素D浓度在接受CD19靶向CAR-T 细胞治疗（CAR-T）的复发/难治性LBCL中的作用目前尚不清楚。这是一项单中心观察性研究，评估了111例成人复发/难治性LBCL患者CAR-T 治疗前25-羟基维生素D（25-OHD）状态与100天完全缓解、无进展生存期、总生存期及CAR-T 相关毒性之间的关联。根据内分泌学会指南，维生素D不足定义为30 ng/mL。CAR-T 治疗前25-羟基维生素D浓度中位数为24 ng/mL（四分位距=18-34）。维生素D不足患者（30 ng/mL；n = 73 [66%]）显著年轻于维生素D充足患者（>30 ng/mL；n = 38 [34%]）（P= .039）。
维生素D不足队列中组织学亚型为新发LBCL的比例更高（P= .026），且CAR-T 产品为tisagenlecleucel的比例更高（P= .049）。两组之间基线特征无其他显著差异。与维生素D充足患者相比，维生素D不足患者的100天完全缓解率为55%对76%（P= .029），2年总生存率为41%对71%（P= .061）。在多变量分析中，维生素D不足仍与100天完全缓解显著相关（比值比2.58 [1.05-6.83]；P= .045）和总生存期显著相关（风险比2.24 [1.08-4.66]，P= .030）。在接受tisagenlecleucel的受者中，维生素D不足与输注的CAR-T 产品细胞活力显著降低相关（P= .015）。
最后，治疗前维生素D不足并不能预测后续CAR-T 相关毒性。这是首个表明维生素D不足与CAR-T 接受者临床结局较差相关的报告。有必要进一步研究这一发现的机制，以及维生素D补充对优化CAR-T 的潜在作用。
展开英文摘要原文
Vitamin D insufficiency is a potentially modifiable risk factor for poor outcomes in newly diagnosed large B-cell lymphoma (LBCL).
However, the role of circulating vitamin D concentrations in relapsed/refractory LBCL treated with CD19-directed chimeric antigen receptor T-cell therapy (CAR-T) is currently unknown. This was a single-center, observational study that evaluated the association of pre-CAR-T 25-hydroxyvitamin D (25-OHD) status with 100-day complete response, progression-free survival, overall survival, and CAR-T-related toxicity in 111 adult relapsed/refractory LBCL patients. Vitamin D insufficiency was defined as 30 ng/mL in accordance with the Endocrine Society guidelines. The median pre-CAR-T 25-hydroxyvitamin D concentration was 24 ng/mL (interquarile range = 18-34). Vitamin D-insufficient patients ( 30 ng/mL; n = 73 [66%]) were significantly younger than their vitamin D-replete (>30 ng/mL; n = 38 [34%]) counterparts (P= . 039).
The vitamin D-insufficient cohort was enriched for de novo LBCL as the histological subtype (P= . 026) and had a higher proportion of tisagenlecleucel as the CAR-T product (P= . 049). There were no other significant differences in the baseline characteristics between the two groups. In vitamin D-insufficient compared to -replete patients, 100-day complete response was 55% versus 76% (P= . 029), and 2-year overall survival was 41% versus 71% (P= .
061), respectively. In multivariate analysis, vitamin D insufficiency remained significantly associated with 100-day complete response (odds ratio 2. 58 [1. 05-6. 83]; P= . 045) and overall survival (hazard ratio 2. 24 [1. 08-4. 66], P= . 030). In recipients of tisagenlecleucel, vitamin D insufficiency was associated with significantly lower cell viability of the infused CAR-T product (P= . 015).
Finally, pretreatment vitamin D insufficiency did not predict for subsequent CAR-T-related toxicity. This is the first report to demonstrate that vitamin D insufficiency is associated with inferior clinical outcomes in CAR-T recipients.
Further study into the mechanistic insights of this finding, and the potential role of vitamin D supplementation to optimize CAR-T are warranted.
论文信息
- 作者
- Nath K、Tomas AA、Flynn J、Fein JA、Alperovich A、Anagnostou T、Batlevi CL、Dahi PB
- 第一作者单位
- Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, New York.United States
- 通讯作者单位
- Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York. Electronic address: shouvalr@mskcc.org.United States
- 文献类型
- 观察性研究 · 美国 NIH 资助研究 · 非美国政府资助研究
- 期刊
- Transplantation and cellular therapy2022 Nov
- 原文标识
- PubMed 35944603 · DOI 10.1016/j.jtct.2022.08.001
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