Long-Term Follow-Up of CD19-CAR T-Cell Therapy in Children and Young Adults With B-ALL
Long-Term Follow-Up of CD19-CAR T-Cell Therapy in Children and Young Adults With B-ALL
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DOI：
10.1200/jco.20.02262
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发表时间：
2021-05-20
影响因子：
45.3
通讯作者：
Mackall, Crystal L.
中科院分区：
文献类型：
--
作者：
Shah, Nirali N.;Lee, Daniel W.;Mackall, Crystal L.
目的CD 19嵌合抗原受体（CD 19-CAR）T细胞在儿童和青年B细胞急性淋巴细胞白血病（B-ALL）患者中诱导高应答率，但复发率高。CD 19-CAR T细胞治疗后异基因造血干细胞移植（alloHSCT）对改善CAYAs长期预后的作用尚未研究。方法我们在复发或难治性B-ALL的CAYAs中进行了自体CD 19. 28 zeta-CAR T细胞的I期试验。反应和长期的临床结果进行了评估与疾病和治疗variable.Results五十CAYA与B-ALL治疗（中位年龄，13.5岁，范围，4.3-30.4）。31例（62.0%）患者达到完全缓解（CR），其中28例（90.3%）患者经流式细胞术检测为微小残留病阴性。与非氟达拉滨/环磷酰胺淋巴清除（2/8，25%; P = 0.041）相比，使用氟达拉滨/环磷酰胺淋巴清除与CR率改善相关（29/42，69%）。中位随访时间为4.8年，中位总生存期为10.5个月（95% CI，6.3 - 29.2个月）。21/28例（75.0%）达到极轻微残留疾病阴性CR的患者继续接受alloHSCT。对于进行alloHSCT的患者，中位总生存期为70.2个月（95% CI，10.4个月至无法估计）。异基因造血干细胞移植后累计复发率为9.5% 24个月时（95% CI，1.5 - 26.8）; alloHSCT后5年EFS为61.9%（95%可信区间，结论：我们提供了迄今为止报道的CD 19-CAR T细胞治疗后CAYA伴B-ALL患者的最长随访时间，并证明了CD 19. 28 zeta. CAR T细胞随后进行alloHSCT可以在相当大比例的CAYA复发性或难治性B-ALL中介导持久的疾病控制。
PURPOSE CD19 chimeric antigen receptor (CD19-CAR) T cells induce high response rates in children and young adults (CAYAs) with B-cell acute lymphoblastic leukemia (B-ALL), but relapse rates are high. The role for allogeneic hematopoietic stem-cell transplant (alloHSCT) following CD19-CAR T-cell therapy to improve long-term outcomes in CAYAs has not been examined.METHODS We conducted a phase I trial of autologous CD19.28 zeta-CAR T cells in CAYAs with relapsed or refractory B-ALL. Response and long-term clinical outcomes were assessed in relation to disease and treatment variables.RESULTS Fifty CAYAs with B-ALL were treated (median age, 13.5 years; range, 4.3-30.4). Thirty-one (62.0%) patients achieved a complete remission (CR), 28 (90.3%) of whom were minimal residual disease-negative by flow cytometry. Utilization of fludarabine/cyclophosphamide-based lymphodepletion was associated with improved CR rates (29/42, 69%) compared with non-fludarabine/cyclophosphamide-based lymphodepletion (2/8, 25%; P = .041). With median follow-up of 4.8 years, median overall survival was 10.5 months (95% CI, 6.3 to 29.2 months). Twenty-one of 28 (75.0%) patients achieving a minimal residual disease-negative CR proceeded to alloHSCT. For those proceeding to alloHSCT, median overall survival was 70.2 months (95% CI, 10.4 months to not estimable). The cumulative incidence of relapse after alloHSCT was 9.5% (95% CI, 1.5 to 26.8) at 24 months; 5-year EFS following alloHSCT was 61.9% (95% CI, 38.1 to 78.8).CONCLUSION We provide the longest follow-up in CAYAs with B-ALL after CD19-CAR T-cell therapy reported to date and demonstrate that sequential therapy with CD19.28 zeta-CAR T cells followed by alloHSCT can mediate durable disease control in a sizable fraction of CAYAs with relapsed or refractory B-ALL.