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
英文原题:CD19-directed CART therapy for T-cell/histiocyte-rich large B-cell lymphoma.
CD19-directed CART therapy for T-cell/histiocyte-rich large B-cell lymphoma.
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T细胞/组织细胞丰富型大B细胞淋巴瘤(THRLBCL)是LBCL的一种罕见组织学变异型。关于CD19靶向CAR-T 细胞治疗复发/难治性(R/R)THRLBCL的有限数据提示疗效不佳。
我们通过国际血液和骨髓移植研究中心注册数据库研究了CAR-T 对R/R THRLBCL的疗效。共纳入58例在2018年至2022年间接受商业化CD19-CART治疗的R/R THRLBCL成人患者。大多数患者(67%)为疾病早期复发(45%原发难治),既往治疗中位数为3线(范围,1-7),并接受axicabtagene ciloleucel治疗(69%)。CAR-T 治疗后中位随访23个月时,2年总生存率和无进展生存率分别为42%(95% CI,27-57)和29%(95% CI,17-43)。在单变量分析中,CAR-T 治疗前体能状态差与更高的死亡率相关(风险比,2.35;95% CI,1.02-5.5)。2年复发/进展和非复发死亡累积发生率分别为69%和2%。≥3级细胞因子释放综合征和免疫效应细胞相关神经综合征分别发生于7%和15%的患者。在这项关于CD19-CART治疗R/R THRLBCL的最大规模分析中,约30%的患者在CAR-T 治疗后2年存活且无进展。尽管进展发生率高(2年时为69%),这些结果提示一部分R/R THRLBCL患者可能通过CAR-T 获得持久缓解。
T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare histologic variant of LBCL. Limited data regarding CD19-directed chimeric antigen receptor T-cell (CART) therapy in relapsed/refractory (R/R) THRLBCL suggest poor efficacy.
We investigated CART outcomes for R/R THRLBCL through the Center for International Blood and Marrow Transplant Research registry. A total of 58 adult patients with R/R THRLBCL who received commercial CD19-CART therapy between 2018 and 2022 were identified. Most patients (67%) had early relapse of disease (45% primary refractory) with a median of 3 (range, 1-7) prior therapies and were treated with axicabtagene ciloleucel (69%). At median follow-up of 23 months after CART therapy, 2-year overall and progression-free survival were 42% (95% confidence interval [CI], 27-57) and 29% (95% CI, 17-43), respectively.
In univariable analysis, poor performance status before CART therapy was associated with higher mortality (hazard ratio, 2. 35; 95%CI, 1. 02-5. 5). The 2-year cumulative incidences of relapse/progression and nonrelapse mortality were 69% and 2%, respectively. Grade ≥3 cytokine release syndrome and immune effector cell-associated neurologic syndrome occurred in 7% and 15% of patients, respectively.
In this largest analysis of CD19-CART therapy for R/R THRLBCL, ∼30% of patients were alive and progression free 2 years after CART therapy. Despite a high incidence of progression (69% at 2 years), these results suggest a subset of patients with R/R THRLBCL may have durable responses with CARTs.
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