小鼠嵌合抗原受体T（CAR-T）细胞疗法已经在复发/难治B细胞急性淋巴细胞白血病（B-ALL）患者中展现出临床益处。然而，小鼠的单链抗体可变区结构域的潜在免疫原性可能会限制CAR-T细胞的持续存在，导致复发。我们进行了一项临床试验，以确定自体和同种异体人源化CD19靶向CAR-T细胞（hCART19）在R/R B-ALL中的安全性和有效性。58名患者（年龄13-74岁）在2020年2月至2022年3月期间接受治疗。终点包括完全缓解率（CR）、总生存期（OS）、事件无发生期生存期（EFS）和安全性。总体上，93.1%（54/58）的患者在28天内达到了CR或CRi，53名患者的最小残留疾病结果为阴性。经过13.5个月的中位随访，估计1年的OS和EFS分别为73.6%（95% CI 62.1%到87.4%）和46.0%（95% CI 33.7%到62.8%），中位OS和EFS分别为21.5个月和9.5个月。输注后没有观察到人类抗小鼠抗体的显著增加（p = 0.78）。血细胞中B细胞减少持续时间长达616天，比我们以前的mCART19试验更长。所有毒性反应都是可逆的，包括36%（21/58）的患者出现严重的细胞因子释放综合征和5%（3/58）的患者出现严重的神经毒性反应。与我们以前的mCART19试验相比，接受hCART19治疗的患者具有较长的EFS，并且毒性增加较少。此外，我们的数据还表明，接受巩固治疗（包括同种异体造血干细胞移植或CD22靶向CAR-T细胞）的患者在接受hCART19治疗后EFS比没有巩固治疗的患者更长。hCART19对R/R B-ALL患者具有良好的短期疗效和可控毒性。NCT04532268。 ©作者（或其雇主（们））2023。在CC BY-NC许可下重新使用。 不得有商业再利用。由BMJ出版。

Murine chimeric antigen receptor T (CAR-T) cell therapy has demonstrated clinical benefit in patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). However, the potential immunogenicity of the murine single-chain variable fragment domain may limit the persistence of CAR-T cell, leading to relapse.We performed a clinical trial to determine the safety and efficacy of autologous and allogeneic humanized CD19-targeted CAR-T cell (hCART19) for R/R B-ALL. Fifty-eight patients (aged 13-74 years) were enrolled and treated between February 2020 and March 2022. The endpoints were complete remission (CR) rate, overall survival (OS), event-free survival (EFS), and safety.Overall, 93.1% (54/58) of patients achieved CR or CR with incomplete count recovery (CRi) by day 28, with 53 patients having minimal residual disease negativity. With a median follow-up of 13.5 months, the estimated 1-year OS and EFS were 73.6% (95% CI 62.1% to 87.4%) and 46.0% (95% CI 33.7% to 62.8%), with a median OS and EFS of 21.5 months and 9.5 months, respectively. No significant increase in human antimouse antibodies was observed following infusion (p=0.78). Duration of B-cell aplasia in the blood was observed for as long as 616 days, which was longer than that in our prior mCART19 trial. All toxicities were reversible, including severe cytokine release syndrome, which developed in 36% (21/58) of patients and severe neurotoxicity, which developed in 5% (3/58) of patients. Compared with our prior mCART19 trial, patients treated with hCART19 had longer EFS without increased toxicity. Additionally, our data also suggest that patients treated with consolidation therapy, including allogeneic hematopoietic stem cell transplantation or CD22-targeted CAR-T cell, following hCART19 therapy had a longer EFS than those without consolidation therapy.hCART19 has good short-term efficacy and manageable toxicity in R/R B-ALL patients.NCT04532268.© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.