Ma R Z, He Y, Yang D L, Wei J L, Pang A M, Jiang E L, Wang J X, Han M Z, Zhang R L, Feng S Z
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
Zhonghua Xue Ye Xue Za Zhi. 2021 May 14;42(5):383-389. doi: 10.3760/cma.j.issn.0253-2727.2021.05.006.
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 leukemia-free 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. 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. Chinese Clinical Trial Registry: ChiCTR1900025419.
为研究供体来源的CD19嵌合抗原受体(CAR)T细胞(HI19α-4-1BB-ζ CAR-T)疗法治疗异基因造血干细胞移植(allo-HSCT)后复发的B细胞急性淋巴细胞白血病(B-ALL)患者的长期疗效和副作用。2017年7月至2020年5月,共有9例allo-HSCT后复发的B-ALL患者接受了供体来源的CD19 CAR-T治疗。所有受试者在淋巴细胞清除化疗后输注供体CD3阳性T细胞,CAR-T细胞的中位剂量为1.79(范围0.86-3.53)×10(6)/kg。①所有受试者在输注CAR-T细胞后28-42天均达到完全缓解且微小残留病(MRD)阴性。②所有受试者均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例受试者发生免疫效应细胞相关神经毒性综合征(ICANS),其中2级1例,1级3例。1例受试者发生Ⅳ级急性移植物抗宿主病(GVHD),且副作用均可控。③4例受试者在中位时间8.6(4.6-19.3)个月时复发,2例受试者在接受化疗后死于疾病进展,另1例在第二次移植后14个月也死于疾病进展,仅1例受试者在接受CD22 CAR-T细胞治疗后达到完全缓解。至最后随访日期,6例受试者无白血病且实现完全供体嵌合。估计1年和2年无白血病生存率(LFS)分别为63.5%和50.8%,中位LFS为18.1个月。④中位随访25.1(范围6.9-36.7)个月后,估计2年和2.5年总生存率(OS)分别为87.5%和52.5%。供体来源的CD19 CAR-T细胞疗法在allo-HSCT后复发的B-ALL患者中获得了较高的缓解率,副作用可耐受,半数受试者存活超过2年且无疾病复发,不过长期疗效仍需进一步观察。中国临床试验注册中心:ChiCTR1900025419。
Cytotherapy. 2018-10-9
N Engl J Med. 2018-2-1