决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:The impact of IPI risk factors on CAR T-cell therapy or allogeneic stem cell transplantation for treatment of relapsed or refractory large B-cell lymphoma (LBCL).
为了比较CAR-T 细胞(CART)治疗和异基因干细胞移植(alloSCT)在IPI风险因素相关的结果,我们分析了515例接受CART(n = 303)或alloSCT(n = 212)作为三线治疗的LBCL患者,这些患者注册于EBMT(2016-2021年)。
国际预后指数(IPI)是大B细胞淋巴瘤(LBCL)患者重要的预后工具。为依据IPI危险因素比较CAR-T 细胞治疗和异基因干细胞移植(alloSCT)后的结局,我们分析了EBMT登记的515例接受三线治疗的LBCL患者,其中303例接受CAR-T,212例接受alloSCT(2016–2021年)。CAR-T组患者年龄较大(中位62.4岁比51.1岁),IPI评分较高(高危/中高危占48.2%比20.8%),难治性疾病发生率也更高(84.1%比34.6%)。24个月时,两组总生存期(OS)分别为49%和41%,无进展生存期(PFS)为37%和32%,复发发生率为56%和38%,非复发死亡率(NRM)为7%和30%。多变量分析显示,CAR-T治疗的OS更优,主要源于NRM显著较低,但复发发生率较高。CAR-T的生存获益在IPI低危/中低危患者中显著(OS HR 0.43,95% CI 0.31–0.60),在高危患者中则未见。LDH升高会消除CAR-T相对于alloSCT的PFS优势。高危疾病患者CAR-T治疗结局不佳,支持对符合条件者尽早准备alloSCT。
The International Prognostic Index (IPI) is an essential prognostic tool for patients with large B-cell lymphoma (LBCL). To compare outcomes after chimeric antigen receptor T-cell (CART) therapy and allogeneic stem cell transplantation (alloSCT) in relation to IPI risk factors, we analyzed 515 LBCL patients receiving CART (n = 303) or alloSCT (n = 212) as third-line treatment, registered with EBMT (2016-2021). Patients treated with CART were older (median 62.4 vs 51.1 years), had higher IPI scores (48.2% vs 20.8% high/high-intermediate risk), and a higher incidence of refractory disease (84.1% vs 34.6%). At 24 months, overall survival (OS) was 49% vs 41%, progression-free survival (PFS) was 37% vs 32%, relapse-incidence (RI) was 56% vs 38%, and non-relapse-mortality (NRM) was 7% vs 30%, respectively. In multivariate analysis, CART therapy showed superior OS primarily due to significantly lower NRM, while RI was higher. The survival benefit of CART was significant in patients with low/low-intermediate IPI (OS HR 0.43, 95% CI 0.31-0.60), but not observed in high-risk patients. Elevated LDH eliminated the PFS advantage of CART over alloSCT. Poor outcomes after CART in patients with high-risk disease support early preparation for alloSCT for eligible patients.
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