研究性 CAR T 细胞疗法治疗复发性和难治性婴儿 ALL 的可行性和良好反应。
Feasibility and Favorable Responses Following Investigational CAR T-Cell Therapy for Relapsed and Refractory Infant ALL.
发表日期：2024 Aug 12
作者：
Colleen Annesley, Adam J Lamble, Corinne Summers, Michael A Pulsipher, Alan S Wayne, Julie Rivers, Wenjun Huang, Ashley Wilson, Qian Wu, Kristy D Seidel, Stephanie Mgebroff, Christopher T Brown, Catherine Lindgren, Julie R Park, Michael C Jensen, Rebecca A Gardner
来源：
Blood Advances
摘要：
与患有 B-ALL 的年龄较大的儿童相比，患有 B 细胞急性淋巴细胞白血病 (B-ALL) 的婴儿的预后仍然明显较差，而那些患有复发性或难治性 (R/R) 婴儿 ALL 的患者在接受常规治疗后的预后尤其糟糕。靶向 CD19 的嵌合抗原受体 (CAR) T 细胞疗法在治疗 R/R 儿童 B-ALL 方面已取得显着成功，尽管大多数报告都是针对非婴儿患者。在婴儿 B-ALL 中成功实施 CAR T 细胞疗法的障碍包括与血浆分离术、产品制造和谱系转换等疾病特定考虑因素相关的挑战。我们描述了我们使用两种实验性 CD19-CAR T 细胞产品 SCRI-CAR19 或 SCRI-CAR19x22 的经验，用于参加三项临床试验的 19 名 R/R 婴儿 B-ALL 患者。 CAR T 细胞产品在 18/19 (94.7%) 的患者中成功生产，入组时的中位年龄为 22.5 个月（范围为 14.5-40.1 个月）。 17 名接受治疗的患者中有 16 名 (94.1%) 达到完全缓解，没有检测到微小残留病。 1年无白血病生存率为75%，1年总生存率为76.5%，中位随访时间为35.8个月（范围1.7-83.6个月）。 14/17 (82.4%) 患者发生细胞因子释放综合征 (CRS)，其中只有 1 名患者出现 3 级 CRS。 2/17 (11.8%) 患者发生神经毒性，所有事件均≤ 2 级。随着 CAR T 细胞治疗在该人群中取得成功的早期临床经验，有必要针对婴儿 ALL 进行更系统的评估。版权所有 © 2024 美国学会血液学。
Infants with B-cell acute lymphoblastic leukemia (B-ALL) continue to have significantly worse outcomes compared to older children with B-ALL, and those with relapsed or refractory (R/R) infant ALL have especially dismal outcomes with conventional treatment. CD19-targeting chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable success in the treatment of R/R childhood B-ALL, though the majority of reports have been in non-infant patients. Barriers to the successful implementation of CAR T-cell therapy in infant B-ALL include challenges related to apheresis, product manufacturing and disease-specific considerations such as lineage switch. We describe our experience utilizing two experimental CD19-CAR T-cell products, SCRI-CAR19 or SCRI-CAR19x22, for 19 patients with R/R infant B-ALL enrolled on three clinical trials. CAR T-cell products were successfully manufactured in 18/19 (94.7%) patients, with a median age of 22.5 months at enrollment (range, 14.5-40.1 months). Sixteen of 17 (94.1%) treated patients achieved a complete remission without detectable minimal residual disease. The 1-year leukemia free survival was 75% and 1-year overall survival was 76.5%, with a median follow up time of 35.8 months (range, 1.7-83.6 months). Cytokine release syndrome (CRS) occurred in 14/17 (82.4%) patients, with only 1 patient experiencing Grade 3 CRS. Neurotoxicity occurred in 2/17 (11.8%) patients with all events ≤ Grade 2. With the successful early clinical experience of CAR T-cell therapy in this population, more systematic evaluation specific to infant ALL is warranted.Copyright © 2024 American Society of Hematology.