Hematology Department, the Second Hospital of Anhui Medical University (SHAMU), Hefei, Anhui Province, China.
Hematologic Diseases Research Center of Anhui Medical University, Hefei, Anhui Province, China.
Nat Commun. 2020 Nov 23;11(1):5928. doi: 10.1038/s41467-020-19774-x.
CD19-specific chimeric antigen receptor T cell (CD19 CAR T) therapy has shown high remission rates in patients with refractory/relapsed B-cell acute lymphoblastic leukemia (r/r B-ALL). However, the long-term outcome and the factors that influence the efficacy need further exploration. Here we report the outcome of 51 r/r B-ALL patients from a non-randomized, Phase II clinical trial (ClinicalTrials.gov number: NCT02735291). The primary outcome shows that the overall remission rate (complete remission with or without incomplete hematologic recovery) is 80.9%. The secondary outcome reveals that the overall survival (OS) and relapse-free survival (RFS) rates at 1 year are 53.0 and 45.0%, respectively. The incidence of grade 4 adverse reactions is 6.4%. The trial meets pre-specified endpoints. Further analysis shows that patients with extramedullary diseases (EMDs) other than central nervous system (CNS) involvement have the lowest remission rate (28.6%). The OS and RFS in patients with any subtype of EMDs, higher Tregs, or high-risk genetic factors are all significantly lower than that in their corresponding control cohorts. EMDs and higher Tregs are independent high-risk factors respectively for poor OS and RFS. Thus, these patient characteristics may hinder the efficacy of CAR T therapy.
CD19 特异性嵌合抗原受体 T 细胞(CD19 CAR T)疗法在难治/复发 B 细胞急性淋巴细胞白血病(r/r B-ALL)患者中显示出高缓解率。然而,其长期疗效和影响疗效的因素仍需要进一步探索。在此,我们报告了一项非随机、Ⅱ期临床试验(ClinicalTrials.gov 编号:NCT02735291)中 51 例 r/r B-ALL 患者的结果。主要结局显示,总体缓解率(完全缓解伴或不伴不完全血液学恢复)为 80.9%。次要结局显示,1 年时的总生存率(OS)和无复发生存率(RFS)分别为 53.0%和 45.0%。4 级不良反应发生率为 6.4%。试验达到了预设的终点。进一步分析显示,除中枢神经系统(CNS)受累外有髓外疾病(EMD)的患者缓解率最低(28.6%)。任何类型 EMD、较高 Tregs 或高危遗传因素的患者的 OS 和 RFS 均显著低于相应的对照组。EMD 和较高的 Tregs 分别是 OS 和 RFS 的独立高危因素。因此,这些患者特征可能会影响 CAR T 疗法的疗效。