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B 细胞急性淋巴细胞白血病成人患者标准治疗 Brexucabtagene Autoleucel 后异基因造血细胞移植:成人急性淋巴细胞白血病 CAR-T 细胞真实世界结局协作组的结果

英文原题:Allogeneic Hematopoietic Cell Transplant Following Standard of Care Brexucabtagene Autoleucel in Adults with B-Cell Acute Lymphoblastic Leukemia: Results from the Real-World Outcomes Collaborative of Chimeric Antigen Receptor T in Adult Acute Lymphoblastic Leukemia.

查看英文原题

Allogeneic Hematopoietic Cell Transplant Following Standard of Care Brexucabtagene Autoleucel in Adults with B-Cell Acute Lymphoblastic Leukemia: Results from the Real-World Outcomes Collaborative of Chimeric Antigen Receptor T in Adult Acute Lymphoblastic Leukemia.

PubMed 2026/06/27(内容时间) Transplant Cell Ther Q1 · IF 4.7(JCR 2025)

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中文摘要

Brexucabtagene autoleucel(brexu-cel)是一种自体抗CD19CAR-T(CAR-T)细胞疗法,已获批用于成人复发/难治性(r/r)B细胞急性淋巴细胞白血病(B-ALL)。尽管治疗结局令人鼓舞,多数成人患者在brexu-cel治疗后仍会复发,提示需要提高应答持久性的策略。其中一种策略是巩固性异基因造血细胞移植(alloHCT)。

我们报告真实世界成人ALL CAR-T 协作研究(ROCCA)中,接受商业化brexu-cel后进行巩固alloHCT的成人B-ALL患者结局。

我们对商业化brexu-cel治疗后处于完全缓解并接受巩固alloHCT、且登记于ROCCA的r/r B-ALL成人患者开展多中心回顾性分析。ROCCA包括美国41家机构,提供2021至2025年brexu-cel治疗成人B-ALL的回顾性数据。排除CAR-T 治疗失败后接受alloHCT者。主要终点为12个月总生存期(OS)和无事件生存期(EFS);次要终点包括复发、非复发死亡(NRM)和移植物抗宿主病(GVHD)。在399例brexu-cel治疗患者中,65例接受巩固alloHCT,其中56例首次接受alloHCT,9例接受第二次alloHCT。首次移植患者中位年龄为34岁,既往治疗较多,中位治疗线数为3线。移植后中位随访11个月,估算的移植后1年OS和EFS分别为79%(95% CI:64–88)和66%(95% CI:51–77)。1年累积复发率为19%,NRM为13%。

急性II–IV级GVHD发生率为18%,III–IV级为4%,中重度慢性GVHD发生率为12%。单变量分析显示,年龄≥40岁与OS较差(HR=4.31,95% CI:1.40–13.3)和EFS较差(HR=3.36,95% CI:1.43–7.91)相关,而清髓预处理与EFS改善相关(HR=0.37,95% CI:0.15–0.93)。第二次alloHCT患者的1年EFS和OS为59%(95% CI:19–85);1年累积NRM为41%,且未记录复发。在这一大型真实世界队列中,brexu-cel后巩固alloHCT可行,并带来令人鼓舞的生存结局、较低复发率和可接受的毒性,首次移植患者尤为如此。这些发现支持将alloHCT作为CAR-T 诱导缓解后的可行巩固策略,并凸显了需要开展前瞻性研究,以优化CAR-T 治疗后患者选择、预处理方案和移植策略。

展开英文摘要原文

Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor T (CAR T) cell therapy approved for adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). Despite encouraging outcomes, the majority of adults relapse following brexu-cel, highlighting the need for strategies to improve the durability of response. One such strategy is consolidative allogeneic stem cell transplant (alloHCT).

Here, we report outcomes of adults with B-ALL who underwent consolidative alloHCT following commercial brexu-cel as part of the Real-World Outcomes Collaborative of CAR-T in Adult ALL (ROCCA).

We performed a retrospective multicenter analysis of adults with R/R B-ALL who underwent consolidative alloHCT in complete remission after commercial brexu-cel and were registered in ROCCA. ROCCA includes 41 US institutions contributing retrospective data for adults with B-ALL treated with brexu-cel between 2021 and 2025. Patients who received alloHCT after CAR T failure were excluded. Primary endpoints were 12-mo overall survival (OS) and event-free survival (EFS); secondary endpoints included relapse, non-relapse mortality (NRM), and graft-versus-host disease (GVHD). Among 399 brexu-cel-treated patients, 65 underwent consolidative alloHCT, including 56 patients who underwent a first alloHCT and nine who underwent second alloHCT. Among recipients of first alloHCT, the median age was 34 yr, and patients were heavily pretreated with a median of three prior lines of therapy.

With a median follow-up of 11 mo post-HCT, the estimated 1-yr post-HCT OS and EFS were 79% (95% CI, 64 to 88) and 66% (95% CI, 51 to 77), respectively. The 1-yr cumulative incidence (CI) of relapse was 19%, and NRM was 13%. Acute grade II to IV GVHD occurred in 18%, grade III to IV in 4%, and moderate-to-severe chronic GVHD in 12%. In univariable analysis, age 40 was associated with inferior OS (HR 4. 31, 95% CI 1. 40 to 13. 3) and EFS (HR 3. 36, 95% CI 1. 43 to 7.

91), whereas myeloablative conditioning was associated with improved EFS (HR 0. 37, 95% CI 0. 15 to 0. 93). Among second alloHCT recipients, 1-yr EFS and OS were 59% (95% CI, 19 to 85). The 1-yr CI NRM was 41% and there were no relapses documented among these patients. In this large real-world cohort, consolidative alloHCT after brexu-cel was feasible and associated with encouraging survival, low relapse rates, and acceptable toxicity, particularly among HCT-naive recipients.

These findings support alloHCT as a viable consolidation strategy following CAR T-induced remission and highlight the need for prospective studies to refine patient selection, conditioning regimens and transplant approaches in the post-CAR T setting.

论文信息

作者
Faramand RG、Zhang A、Roloff GW、Aldoss I、Advani AS、Battiwalla M、Boccucci J、Byrd K
单位
Moffitt Cancer Center, Tampa, Florida. Electronic address: rawan.faramand@moffitt.org.United States
期刊
Transplantation and cellular therapy2026 Jun 27
原文标识
PubMed 42364734 · DOI 10.1016/j.jtct.2026.06.039