抗CD19嵌合抗原受体T细胞IM19在B细胞肿瘤中的安全性及疗效研究

Efficacy and safety of anti-CD 19 chimeric antigen receptor T cells IM19 in B cell hematologic malignancies

目的:评价抗CD19嵌合抗原受体T(chimeric antigen receptor T,CAR-T)细胞IM19在复发难治B细胞血液系统恶性肿瘤中的疗效及安全性。方法:12例复发难治B细胞血液系统恶性肿瘤患者接受IM19治疗,包括6例B细胞非霍奇金淋巴瘤和6例急性B淋巴细胞白血病患者。患者接受3×10~5～10×10~5cells·kg^(-1)CAR-T细胞输注。细胞回输后1和3个月评估疗效,并监测不良反应事件的发生情况,同时检测细胞扩增以及细胞因子释放。结果:12例患者中有11例达到完全缓解,患者体内可以检测到IM19扩增,以及白介素-6和白介素-10水平升高。没有患者发生≥3级的细胞因子释放综合征和CAR-T细胞相关的神经系统毒性。结论:IM19治疗复发难治B细胞血液系统恶性肿瘤安全有效。

Objective: To investigate the therapeutic efficacy and adverse events of IM19 chimeric antigen receptor T cells in relapsed or refractory B cell hematologic malignancies. Methods: Twelve patients with relapsed or refractory B-cell malignancies, including six B cell Non-Hodgkin lymphoma and six acute lymphoblastic leukemia patients, received IM 19 infusion at dose of 3 × 10^5 ~ 10 × 10^5 cells · kg^-1 IM19. All patients were followed up by monitoring tumor burden ( at 1 and 3 month after infusion), CAR-T persistence, cytokines and adverse events. Results: All but one patients achieved complete remission. IM 19 cells proliferated in vivo and were detectable in the blood. Cytokines including interleukin (IL)-6 and IL-10 were increased after CAR-T infusion. No severe cytokine release syndrome ( CRS )(≥grade 3 ) or CAR-T cell-related encephalopathy syndrome ( CRES )(≥ grade 3 ) occurred. Conclusion : IM 19 is associated with a high remission rate and tolerable toxicities.