Department of Hematology, Hospital Clínic de Barcelona, Barcelona, Spain.
Department of Hematology/Oncology, Hospital Sant Joan de Déu, Barcelona, Spain; Institut de Recerca Pediàtrica Sant Joan de Déu, Barcelona, Spain.
Mol Ther. 2021 Feb 3;29(2):636-644. doi: 10.1016/j.ymthe.2020.09.027. Epub 2020 Sep 20.
We evaluated the administration of ARI-0001 cells (chimeric antigen receptor T cells targeting CD19) in adult and pediatric patients with relapsed/refractory CD19 malignancies. Patients received cyclophosphamide and fludarabine followed by ARI-0001 cells at a dose of 0.4-5 × 10 ARI-0001 cells/kg, initially as a single dose and later split into 3 fractions (10%, 30%, and 60%) with full administration depending on the absence of cytokine release syndrome (CRS). 58 patients were included, of which 47 received therapy: 38 with acute lymphoblastic leukemia (ALL), 8 with non-Hodgkin's lymphoma, and 1 with chronic lymphocytic leukemia. In patients with ALL, grade ≥3 CRS was observed in 13.2% (26.7% before versus 4.3% after the amendment), grade ≥3 neurotoxicity was observed in 2.6%, and the procedure-related mortality was 7.9% at day +100, with no procedure-related deaths after the amendment. The measurable residual disease-negative complete response rate was 71.1% at day +100. Progression-free survival was 47% (95% IC 27%-67%) at 1 year: 51.3% before versus 39.5% after the amendment. Overall survival was 68.6% (95% IC 49.2%-88%) at 1 year. In conclusion, the administration of ARI-0001 cells provided safety and efficacy results that are comparable with other academic or commercially available products. This trial was registered as ClinicalTrials.gov: NCT03144583.
我们评估了 ARI-0001 细胞（靶向 CD19 的嵌合抗原受体 T 细胞）在复发/难治性 CD19 恶性肿瘤的成人和儿科患者中的应用。患者接受环磷酰胺和氟达拉滨治疗后，给予剂量为 0.4-5×10 ARI-0001 细胞/kg 的 ARI-0001 细胞，最初为单次剂量，后来根据是否存在细胞因子释放综合征（CRS）分为 3 个部分（10%、30%和 60%）进行全剂量给药。共纳入 58 例患者，其中 47 例接受了治疗：38 例急性淋巴细胞白血病（ALL），8 例非霍奇金淋巴瘤，1 例慢性淋巴细胞白血病。在 ALL 患者中，≥3 级 CRS 的发生率为 13.2%（修订前为 26.7%，修订后为 4.3%），≥3 级神经毒性的发生率为 2.6%，100 天时与治疗相关的死亡率为 7.9%，修订后无与治疗相关的死亡。100 天时可测量残留疾病阴性完全缓解率为 71.1%。1 年时无进展生存率为 47%（95%CI：27%-67%）：修订前为 51.3%，修订后为 39.5%。1 年总生存率为 68.6%（95%CI：49.2%-88%）。总之，ARI-0001 细胞的给药结果具有安全性和疗效，与其他学术或商业可用产品相当。该试验在 ClinicalTrials.gov 上注册：NCT03144583。
