供者CD19 CAR-T细胞治疗急性B淋巴细胞白血病移植后复发九例临床观察 Translated title: Allogeneic donor-derived CD19 CAR-T therapy of relapsed B-cell acute lmphoblastic leukemia after allogeneic hematopoietic stem cell transplantation

Abstract

目的

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。

方法

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。

结果

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％。

结论

供者抗CD19 CAR-T细胞治疗allo-HSCT后复发的B-ALL的缓解率高，不良反应可耐受，半数患者可无病生存2年以上，长期疗效有待进一步观察。

Translated abstract

Objective

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）.

Methods

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.

Results

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.

Conclusion

The donor-derived CD19 CAR-T cell therapy obtain a high remission rate in relapsed B-ALL patients post allo-HSCT with tolerable side effects, half subjects survived more than 2 years without disease recurrence, though long-term efficacy requires further observation.