印度床旁生产抗 CD19 CAR-T 细胞疗法的安全性、疗效与总成本：VELCART 试验

Decentralized or point-of-care (POC) manufacture of CAR-T cells is a potential strategy to improve accessibility and reduce cost and logistic challenges. A total of 10 relapsed/refractory patients (B cell acute lymphoblastic leukemia [B-ALL] N = 6, diffuse large B cell lymphoma [DLBCL] N = 4) were enrolled in this POC phase 1 study. Chimeric antigen receptor (CAR)-T cells were manufactured using the fully automated CliniMACS Prodigy system. The CAR-T cell products had a median 15-fold expansion with a median transduction rate of 38%. The immunophenotypic characterization indicates a significant increase in central memory and effector T cells.

All the patients were infused with fresh CAR-T cells. Complete remission rates were 100% for B-ALL and 50% for DLBCL. At a median follow-up of 15 months, 8 of 10 patients remain without disease progression. Adverse events reported were cytokine release syndrome grade 2 or higher in 2 of 10 patients.

None of the patients developed immune effector cell-associated neurotoxicity syndrome. Late hematological toxicity of grade 2 or higher was noted only in one patient. Evaluation of health care resource utilization demonstrates that the median cost was US$12,724, while the manufacturing cost was US$35,107.

Our data highlight the safety, efficacy, low cost, and potential to enhance the accessibility of CAR-T cell therapy in low- and middle-income countries through a fully automated and closed manufacturing platform.