Xin Xiangke, Lin Li, Yang Yang, Wang Na, Wang Jue, Xu Jinhuan, Wei Jia, Huang Liang, Zheng Miao, Xiao Yi, Meng Fankai, Cao Yang, Zhu Xiaojian, Zhang Yicheng
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei, China.
Cytotherapy. 2024 May;26(5):456-465. doi: 10.1016/j.jcyt.2024.01.012. Epub 2024 Feb 19.
The combination therapy of autologous hematopoietic stem cell transplantation (ASCT) and chimeric antigen receptor T-cell (CART) therapy has been employed to improve outcomes for relapsed or refractory (R/R) B-cell non-Hodgkin-lymphoma (B-NHL). The widely used conditioning regimen before ASCT plus CART therapy reported in the literature was carmustine, etoposide, cytarabine and melphalan (BEAM). However, whether adding fludarabine to the BEAM regimen (BEAMF) can improve the survival of patients with R/R B-NHL remains unknown.
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.
自体造血干细胞移植(ASCT)与嵌合抗原受体T细胞(CART)疗法的联合应用已用于改善复发或难治性(R/R)B细胞非霍奇金淋巴瘤(B-NHL)的治疗效果。文献报道的ASCT联合CART治疗前广泛使用的预处理方案是卡莫司汀、依托泊苷、阿糖胞苷和美法仑(BEAM)。然而,在BEAM方案中加入氟达拉滨(BEAMF)是否能提高R/R B-NHL患者的生存率仍不清楚。
共纳入39例和19例R/R B-NHL患者,分别比较ASCT联合CD19/22 CART治疗前BEAM方案和BEAMF方案的临床疗效。
ASCT联合CD19/22 CART治疗前,BEAM方案和BEAMF方案3个月时的客观缓解(OR)率分别为71.8%和94.7%(P = 0.093)。与BEAM方案相比,BEAMF方案的缓解持续时间有延长趋势(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方案的2年无进展生存期(PFS)更优(89.5%对63.9%;P = 0.048),2年总生存期(OS)也更优(100%对77.3%;P = 0.035)。在多变量Cox回归分析中,与OR(未缓解者)相比,3个月时的OR(缓解者)与更好的OS显著相关(风险比:0.112,P = 0.005)。
对于R/R B-NHL患者,ASCT联合CD19/22 CART治疗前的BEAMF方案与比BEAM方案更优的PFS和OS相关,且BEAMF方案是ASCT联合CAR-T治疗有前景的替代预处理方案。