观察供者抗CD19嵌合抗原受体T细胞(CAR-T)(HI19α-4-1BB-ζ CAR-T)治疗急性B淋巴细胞白血病(B-ALL)异基因造血干细胞移植(allo-HSCT)后复发患者的疗效及安全性。
对2017年7月至2020年5月期间9例allo-HSCT后复发B-ALL患者应用供者抗CD19 CAR-T细胞治疗,FCA方案(氟达拉滨+环磷酰胺+阿糖胞苷)预处理后回输供者CD3 +T淋巴细胞,其中CAR-T细胞中位数1.79(0.86~3.53)×10 6/kg,观察疗效和不良反应。
①输注CAR-T细胞后28~42 d,9例患者均获得MRD阴性的完全缓解。②所有患者发生细胞因子释放综合征(CRS),其中3级2例、2级4例、1级3例;4例患者出现免疫效应细胞相关的神经毒性(ICANS),2级1例、1级3例;1例患者发生急性Ⅳ度移植物抗宿主病(GVHD),上述不良反应经治疗均控制。③4例患者再次复发,中位复发时间为CAR-T细胞治疗后8.6(4.6~19.3)个月,2例化疗后病情进展死亡,1例接受二次移植14个月后复发死亡,1例接受CD22 CAR-T细胞治疗后完全缓解,现6例患者无病存活,植入分析为完全供者嵌合体,中位无白血病生存(LFS)期18.1个月,预期1年、2年LFS率分别为63.5%、50.8%。④中位随访25.1(6.9~36.7)个月,预期2年、2.5年总生存(OS)率分别为87.5%、52.5%。
To investigate the long term efficacy and side effects of a donor-derived CD19 chimeric antigen receptor(CAR)T-cell(HI19α-4-1BB-ζ CAR-T)therapy in the treatment of patients with relapsed B-cell acute lymphoblastic leukemia(B-ALL)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).
A total of 9 subjects with relapsed B-ALL post allo-HSCT received donor-derived CD19 CAR-T therapy from July 2017 to May 2020. All subjects were infused with donor CD3-positive T cells after lymphodepletion chemotherapy, and a median dose of CAR-T cells was 1.79(range, 0.86–3.53)×10 6/kg.
①All subjects achieved complete remission and MRD-negative at 28–42 d post CAR-T cells infusion. ②Cytokine releasing syndrome(CRS)occurrd in all subjects and was grade 3 in 2, grade 2 in 4, grade 1 in 3 cases respectively. Four subjects developed immune effector cell-associated neurotoxicity syndrome(ICANS), which was grade 2 in 1, grade 1 in 3. One subject developed grade IV acute graft-versus-host disease(GVHD), and side effects were all controllable. ③Four subjects relapsed at a median period of 8.6(4.6–19.3)months, 2 subjects died of disease progression after receiving chemotherapy and another one also died of disease progression 14 months after a second transplant, only 1 subject achieved complete remission after CD22 CAR-T cell therapy. Until last follow-up date, 6 subjects were leukemia-free and achieved complete donor chimerism. The estimated 1-year and 2-year leukemiafree survival(LFS)rate was 63.5% and 50.8%, with a median LFS of 18.1 months. ④After a median follow-up of 25.1(range, 6.9–36.7)months, the estimated 2-year and 2.5-year OS rate were 87.5% and 52.5%, respectively.