[Clinical analysis of long-term survival and influencing factors of chimeric antigen receptor T-cell therapy in relapsed/refractory acute B-cell lymphoblastic leukemia]

Zhonghua Xue Ye Xue Za Zhi. 2023 Oct 14;44(10):800-804. doi: 10.3760/cma.j.issn.0253-2727.2023.10.002.
[Article in Chinese]

Abstract

Objective: To analyze the survival and influencing factors of chimeric antigen receptor (CAR) T-cell therapy in relapsed/refractory acute B-cell lymphoblastic leukemia (R/R B-ALL) . Methods: Clinical information of patients who received CAR-T-cell therapy and achieved complete remission of R/R B-ALL between May 2015 and June 2018 at the Shaanxi Provincial People's Hospital was obtained. Kaplan-Meier analysis was used to evaluate the overall survival (OS) and leukemia-free survival (LFS) times of patients, and Cox regression analysis was performed to analyze the prognostic factors that affect patient survival after CAR-T therapy. Results: Among the 38 patients with R/R B-ALL, 21 were men, with a median age of 25 (6-59) years and a median OS time of 18 (95% CI 3-33) months. Multivariate Cox regression analysis showed that positive MLL-AF4 fusion gene expression was an independent risk factor for OS and LFS (OS: HR=4.888, 95% CI 1.375-17.374, P=0.014; LFS: HR=6.683, 95% CI 1.815-24.608, P=0.004). Maintenance therapy was a protective factor for OS and LFS (OS: HR=0.153, 95% CI 0.054-0.432, P<0.001; LFS: HR=0.138, 95% CI 0.050-0.382, P<0.001). In patients with MRD negative conversion, LFS benefit (HR=0.209, 95% CI 0.055-0.797, P=0.022) and OS difference was statistically insignificant (P=0.111). Moreover, patients with high tumor burden were risk factors for OS and LFS at the level of 0.1 (OS: HR=2.662, 95% CI 0.987-7.184, P=0.053; LFS: HR=2.452, 95% CI 0.949-6.339, P=0.064) . Conclusion: High tumor burden and high-risk genetics may affect the long-term survival rate of patients with R/R B-ALL receiving CAR-T, and lenalidomide-based maintenance therapy may improve their prognosis.

目的: 分析嵌合抗原受体T细胞(CAR-T)治疗复发/难治急性B淋巴细胞白血病(R/R B-ALL)获完全缓解(CR)患者的长期生存及其影响因素。 方法: 收集2015年5月至2018年7月就诊于陕西省人民医院接受靶向CD19的CAR-T细胞治疗并获得CR的R/R B-ALL患者的临床信息。采用Kaplan-Meier法评估患者的总生存(OS)和无白血病生存(LFS),并通过Cox等比例风险回归分析CAR-T治疗后患者预后的影响因素。 结果: 纳入的38例R/R B-ALL患者中,男性患者21例,中位年龄25(6~59)岁,中位OS时间为18(95%CI 3~33)个月。多因素Cox回归分析显示:MLL-AF4融合基因阳性是OS及LFS的独立危险因素(OS:HR=4.888,95% CI 1.375~17.374,P=0.014;LFS:HR=6.683,95%CI 1.815~24.608,P=0.004);接受维持治疗是OS及LFS的独立保护因素(OS:HR=0.153,95%CI 0.054~0.432,P<0.001;LFS:HR=0.138,95%CI 0.050~0.382,P<0.001);MRD转阴患者LFS获益(HR=0.209,95%CI 0.055~0.797,P=0.022),但OS差异无统计学意义(P=0.111);具有高肿瘤负荷的患者在0.1的水平上是OS及LFS的危险因素(OS:HR=2.662,95%CI 0.987~7.184,P=0.053;LFS:HR=2.452,95%CI 0.949~6.339,P=0.064)。 结论: 高肿瘤负荷和高危遗传学可能会影响R/R B-ALL患者接受CAR-T治疗后的长期生存,予以来那度胺为基础的维持治疗有可能改善患者的长期预后。.

Keywords: Acute lymphoblastic leukemia; Chimeric antigen receptor-modified T cell; Prognosis; Relapsed/ refractory.

Publication types

  • English Abstract

MeSH terms

  • Adult
  • Cell- and Tissue-Based Therapy
  • Female
  • Humans
  • Immunotherapy, Adoptive
  • Male
  • Middle Aged
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / therapy
  • Receptors, Chimeric Antigen* / genetics

Substances

  • Receptors, Chimeric Antigen