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:Prognostic differences between carmustine, etoposide, cytarabine and melphalan (BEAM) and carmustine, etoposide, cytarabine, melphalan and fludarabine (BEAMF) regimens before autologous stem cell transplantation plus chimeric antigen receptor T therapy in patients with refractory/relapsed B-cell non-Hodgkin-lymphoma.
Prognostic differences between carmustine, etoposide, cytarabine and melphalan (BEAM) and carmustine, etoposide, cytarabine, melphalan and fludarabine (BEAMF) regimens before autologous stem cell transplantation plus chimeric antigen receptor T therapy in patients with refractory/relapsed B-cell non-Hodgkin-lymphoma.
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对于 R/R B-NHL 患者,ASCT 前采用 BEAMF 方案联合 CD19/22 CAR-T 治疗相比 BEAM 方案与更优的 PFS 和 OS 相关,BEAMF 方案是 ASCT 联合 CAR-T 治疗的一种有前景的替代预处理方案。
自体造血干细胞移植(ASCT)联合CAR-T 细胞治疗已被用于改善复发/难治性(R/R)B细胞非霍奇金淋巴瘤(B-NHL)患者的预后。文献报道中,ASCT联合CAR-T 治疗前广泛使用的预处理方案为卡莫司汀、依托泊苷、阿糖胞苷和马法兰(BEAM)。然而,在BEAM方案中加入氟达拉滨(BEAMF)能否改善R/R B-NHL患者的生存尚不清楚。
总共纳入39例和19例R/R B-NHL患者,分别比较ASCT联合CD19/22 CAR-T 治疗前BEAM方案与BEAMF方案的临床结局。
ASCT前BEAM与BEAMF方案联合CD19/22 CAR-T 治疗的3个月客观缓解(OR)率分别为71.8%和94.7%(P = 0.093)。与BEAM方案相比,BEAMF方案在缓解持续时间方面显示出更优的趋势(P = 0.09)。中位随访28个月(范围:0.93-51.9个月)后,与BEAM方案相比,BEAMF方案显示出更优的2年无进展生存期(PFS)(89.5% vs 63.9%;P = 0.048)和2年总生存期(OS)(100% vs 77.3%;P = 0.035)。在多变量Cox回归分析中,与OR(非缓解者)相比,第3个月OR(缓解者)与更好的OS显著相关(风险比:0.112,P = 0.005)。
In total, 39 and 19 patients with R/R B-NHL were enrolled to compare clinical outcomes in the BEAM and BEAMF regimens before ASCT plus CD19/22 CART therapy, respectively.
The objective response (OR) rates at 3 months to BEAM and BEAMF regimens before ASCT plus CD19/22 CART therapy were 71.8% and 94.7%, respectively (P = 0.093). The BEAMF regimen showed a trend towards a superior duration of response compared with the BEAM regimen (P = 0.09). After a median follow-up of 28 months (range: 0.93-51.9 months), the BEAMF regimen demonstrated superior 2-year progression-free survival (PFS) (89.5% versus 63.9%; P = 0.048) and 2-year overall survival (OS) (100% vs 77.3%; P = 0.035) compared with the BEAM regimen. In the multivariable Cox regression analysis, OR at month 3 (responders) was remarkably correlated with better OS (hazard ratio: 0.112, P = 0.005) compared with OR (non-responders).
For patients with R/R B-NHL, the BEAMF regimen before ASCT plus CD19/22 CART therapy was correlated with superior PFS and OS than the BEAM regimen, and the BEAMF regimen is a promising alternative conditioning regimen for ASCT plus CAR-T therapy.
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