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
CAR-T 细胞输注后早期 CAR(-) CD4(+) T 淋巴细胞恢复：弥漫大 B 细胞淋巴瘤中更差的结局
英文原题：Early CAR(-) CD4(+) T-lymphocytes recovery following CAR-T cell infusion: A worse outcome in diffuse large B cell lymphoma.
查看英文原题
Early CAR(-) CD4(+) T-lymphocytes recovery following CAR-T cell infusion: A worse outcome in diffuse large B cell lymphoma.
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中文摘要
CAR-CD4⁺ T细胞淋巴细胞减少是CAR-T 细胞治疗后新出现的问题。我们分析了31例接受商业CAR-T 治疗的弥漫大B细胞淋巴瘤（DLBCL）或套细胞淋巴瘤患者CD4⁺ T细胞恢复的决定因素，以及其与生存的潜在关联。采用多参数流式细胞术分析循环免疫亚群。CAR-CD4⁺ T细胞恢复至≥200个细胞/μL的6个月累积发生率为0.43（95% CI：0.28–0.65）。在可能影响CD4⁺ T细胞恢复的因素中，与CD28产品（axicabtagene/brexucabtagene，AXI/BRX）相比，输注4-1BB产品tisagenlecleucel（TSA）与CD4⁺ T细胞恢复相关（风险比[HR] 5.79，95% CI 1.16–24.12；p=0.016）。第1、2和3个月时，TSA组CD4⁺ T细胞计数较高。长期CD4⁺ T细胞淋巴细胞减少期间记录到中重度感染。在DLBCL队列中，第1个月早期CD4⁺ T细胞恢复与较差结局相关，多变量总生存期回归模型也支持这一结果（HR=4.46，95% CI 1.12–17.71；p=0.03）。
我们得出结论，与AXI/BRX相比，TSA与更快CAR-CD4⁺ T细胞恢复相关。DLBCL患者第1个月CAR-CD4⁺ T细胞亚群恢复可能是CAR-T 治疗失败的“警示信号”。
展开英文摘要原文
CAR - CD4 + T cell lymphopenia is an emerging issue following CAR-T cell therapy.
We analyzed the determinants of CD4 + T cell recovery and a possible association with survival in 31 consecutive patients treated with commercial CAR-T for diffuse large B-cell (DLBCL) or mantle cell lymphoma. Circulating immune subpopulations were characterized through multiparametric-flow cytometry. Six-month cumulative incidence of CAR - CD4 + T cell recovery ( 200 cells/ L) was 0. 43 (95% confidence interval [CI]: 0. 28-0. 65).
Among possible determinants of CD4 + T cell recovery, we recognized infusion of a 4-1BB product (tisagenlecleucel, TSA) in comparison with a CD28 (axicabtagene/brexucabtagene, AXI/BRX) (hazard ratio [HR] [95% CI]: 5. 79 [1. 16-24. 12] p = 0. 016). Higher CD4 + T cell counts resulted with TSA at month-1, -2 and -3.
Moderate-to-severe infections were registered with prolonged CD4 + T cell lymphopenia. Early, month-1 CD4 + T cell recovery was associated with a worse outcome in the DLBCL cohort, upheld in a multivariate regression model for overall survival (HR: 4. 46 [95% CI: 1. 12-17. 71], p = 0. 03).
We conclude that a faster CAR - CD4 + T cell recovery is associated with TSA as compared to AXI/BRX. Month-1 CAR - CD4 + T cell subset recovery could represent a "red flag" for CAR-T cell therapy failure in DLBCL patients.
论文信息
- 作者
- Gambella M、Carlomagno S、Mangerini R、Colombo N、Parodi A、Ghiggi C、Giannoni L、Coviello E
- 单位
- Ematologia e Terapie Cellulari IRCCS Ospedale Policlinico San Martino Genova Italy.Italy
- 期刊
- EJHaem2024 Apr
- 原文标识
- PubMed 38633118 · DOI 10.1002/jha2.871
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