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
英文原题:Chimeric antigen receptor T-cell therapy for high-grade B-cell lymphoma NOS.
Chimeric antigen receptor T-cell therapy for high-grade B-cell lymphoma NOS.
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CD19 CAR-T 细胞疗法基于大量临床试验,是大 B 细胞淋巴瘤(LBCL)二线和三线治疗算法中的关键组成部分。然而,这些研究纳入的高级别 B 细胞淋巴瘤,非特指型(HGBCL-NOS)患者极少,目前尚不清楚其结局是否与更常见的 LBCL 组织学类型所观察到的结果相似。利用国际血液和骨髓移植研究中心(CIBMTR)登记数据库,我们识别了 111 例接受 CAR-T 治疗的 HGBCL-NOS 患者。细胞因子释放综合征(CRS)发生率为 74%(7.7% 为 3 级及以上),中位发生时间为 4 天(1-17),免疫效应细胞相关神经毒性综合征发生率为 45.2%(22.6% 为 3 级及以上),中位发生时间为 7 天(1-17)。CAR-T 输注后 2 年,总生存率和无进展生存率的概率分别为 41.6% 和 28.7%。2 年非复发死亡率和复发/进展率分别为 3.1%(95% 置信区间 [CI]:0.6-7.6)和 68.1%(95% CI:57.9-77.6)。
我们的分析表明,HGBCL-NOS 患者是一个特别难以治疗的人群,即使采用 CAR-T 疗法也是如此。我们观察到三分之一的患者获得了持久缓解;然而,与已发表的 LBCL 报告相比,总体结果较差,总缓解率、总生存率和无进展生存率均较低。
CD19 chimeric antigen receptor T-cell (CAR-T) therapy is a pivotal part of the treatment algorithm for large B-cell lymphoma (LBCL) in the second- and third-line settings based on numerous clinical trials.
However, these studies included very few patients with a diagnosis of high-grade B-cell lymphoma, not otherwise specified (HGBCL-NOS) and it is unclear if outcomes are similar to those observed with more common LBCL histologies. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, we identified 111 HGBCL-NOS patients who received CAR-T therapy. The cytokine release syndrome (CRS) rate was 74% (7.
7% grade 3+), median onset was 4 days (1-17) and immune effector cell-associated neurotoxicity syndrome rate was 45. 2% (22. 6% grade 3+), median onset was 7 days (1-17). At 2 years post-CAR-T infusion, the probability of overall survival and progression-free survival were 41. 6% and 28. 7% respectively. The 2-year non-relapse mortality and relapse/progression were 3. 1% (95% confidence interval [CI]: 0. 6-7. 6) and 68. 1% (95% CI: 57. 9-77. 6) respectively.
Our analysis illustrates that patients with HGBCL-NOS represent a particularly difficult group to treat, even with CAR-T therapy.
We observed that one third of patients achieved a durable response; however, the overall results were less favourable, with lower overall response rate, overall survival and progression-free survival as compared to published reports on LBCL.
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