Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking-Tsinghua Center for Life Science, Research Unit of Key Technique for Diagnosis and Treatment of Hematologic Malignancies, Chinese Academic of Medical Sciences, Beijing, China.
Department of Pediatrics, Peking University People's Hospital, Peking University, Beijing, China.
Leukemia. 2021 Nov;35(11):3092-3100. doi: 10.1038/s41375-021-01236-y. Epub 2021 Apr 6.
Although chimeric antigen receptor T-cell (CAR-T) therapy produces a high complete remission rate among patients with relapsed/refractory B-cell acute lymphoblastic leukemia, relapse remains an urgent issue. It is uncertain whether consolidative haploidentical-allogeneic hematopoietic stem cell transplantation (haplo-HSCT) is suitable for achieving sustainable remission. Therefore, we aimed to assess the efficacy and safety of bridging CAR-T therapy to haplo-HSCT. Fifty-two patients with relapsed/refractory Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia who underwent haplo-HSCT after CAR-T therapy were analyzed. The median time from CAR-T therapy to haplo-HSCT was 61 days. After a median follow-up of 24.6 months, the 1-year probabilities of event-free survival, overall survival, and cumulative incidence of relapse were 80.1% (95% confidence interval (CI), 69.0-90.9), 92.3% (95% CI, 85.0-99.5), and 14.1% (95% CI, 10.7-17.4), respectively, while the corresponding 2-year probabilities were 76.0% (95% CI, 64.2-87.7), 84.3% (95% CI, 74.3-94.3), and 19.7% (95% CI, 15.3-24.0), respectively. No increased risk of 2-year cumulative incidence of graft-versus-host disease, treatment-related mortality, or infection was observed. A pre-HSCT measurable residual disease-positive status was an independent factor associated with poor overall survival (hazard radio: 4.201, 95% CI: 1.034-17.063; P = 0.045). Haplo-HSCT may be a safe and effective treatment strategy to improve event-free survival and overall survival after CAR-T therapy.
尽管嵌合抗原受体 T 细胞(CAR-T)疗法可使复发/难治性 B 细胞急性淋巴细胞白血病患者获得高完全缓解率,但复发仍是一个紧迫的问题。尚不确定巩固性单倍体相合异基因造血干细胞移植(haplo-HSCT)是否适合实现持续缓解。因此,我们旨在评估 CAR-T 治疗桥接至 haplo-HSCT 的疗效和安全性。分析了 52 例接受 CAR-T 治疗后行 haplo-HSCT 的复发/难治性费城染色体阴性 B 细胞急性淋巴细胞白血病患者。从 CAR-T 治疗到 haplo-HSCT 的中位时间为 61 天。中位随访 24.6 个月后,无事件生存、总生存和累积复发率的 1 年概率分别为 80.1%(95%可信区间[CI],69.0-90.9)、92.3%(95% CI,85.0-99.5)和 14.1%(95% CI,10.7-17.4),相应的 2 年概率分别为 76.0%(95% CI,64.2-87.7)、84.3%(95% CI,74.3-94.3)和 19.7%(95% CI,15.3-24.0)。未观察到 2 年累积移植物抗宿主病、治疗相关死亡率或感染风险增加。HSCT 前可测量残留病阳性状态是总生存不良的独立相关因素(危险比:4.201,95% CI:1.034-17.063;P=0.045)。haplo-HSCT 可能是一种安全有效的治疗策略,可提高 CAR-T 治疗后的无事件生存和总生存。