Efficacy and safety of CD19-specific CAR T cell-based therapy in B-cell acute lymphoblastic leukemia patients
Efficacy and safety of CD19-specific CAR T cell-based therapy in B-cell acute lymphoblastic leukemia patients
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基于 CD19 特异性 CAR T 细胞治疗 B 细胞急性淋巴细胞白血病 CNSL 患者的疗效和安全性
DOI：
10.1182/blood.2021013733
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发表时间：
2022-06-09
期刊：
影响因子：
20.3
通讯作者：
Xu, Kailin
中科院分区：
文献类型：
--
作者：
Qi, Yuekun;Zhao, Mingfeng;Xu, Kailin
由于担心反应不佳和治疗相关的神经毒性，很少有研究描述嵌合抗原受体 (CAR) T 细胞治疗 B 细胞急性淋巴细胞白血病 (B-ALL) 合并中枢神经系统白血病 (CNSL) 患者。我们的研究纳入了 48 名患有 CNSL 的复发/难治性 B-ALL 患者，以评估基于 CD19 特异性 CAR T 细胞疗法的有效性和安全性。输注使骨髓 (BM) 疾病的总体缓解率为 87.5%（95% 置信区间 [CI]，75.3-94.1），CNSL 的缓解率为 85.4%（95% CI，72.8-92.8）。中位随访时间为 11.5 个月（范围 1.3-33.3），中位无事件生存期为 8.7 个月（95% CI，3.7-18.8），中位总生存期为 16.0 个月（95% CI，13.5-20.1）。 12个月时BM和CNS疾病的累积复发率分别为31.1%和11.3%（P<5.040）。治疗总体耐受性良好，9 名患者 (18.8%) 出现 3 级以上细胞因子释放综合征。 11 名患者（22.9%）发生 3 至 4 级神经毒性事件，与输注前中枢神经系统疾病负担较高相关，并在强化管理下得到有效控制。我们的结果表明，基于 CD19 特异性 CAR T 细胞的疗法可以在 BM 和 CNS 疾病中诱导类似的高反应率。 CNSL 的缓解持续时间比 BM 疾病的缓解持续时间长。 CD19 CAR T 细胞疗法可能为之前被排除的 CNSL 患者提供潜在的治疗选择，且神经毒性可控。
Few studies have described chimeric antigen receptor (CAR) T-cell therapy for patients with B-cell acute lymphoblastic leukemia (B-ALL) with central nervous system leukemia (CNSL) because of concerns regarding poor response and treatment-related neurotoxicity. Our study included 48 patients with relapsed/refractory B-ALL with CNSL to evaluate the efficacy and safety of CD19-specific CAR T cell-based therapy. The infusion resulted in an overall response rate of 87.5% (95% confidence interval [CI], 75.3-94.1) in bone marrow (BM) disease and remission rate of 85.4% (95% CI, 72.8-92.8) in CNSL. With a median follow-up of 11.5 months (range, 1.3-33.3), the median event-free survival was 8.7 months (95% CI, 3.7-18.8), and the median overall survival was 16.0 months (95% CI, 13.5-20.1). The cumulative incidences of relapse in BM and CNS diseases were 31.1% and 11.3%, respectively, at 12 months (P 5.040). The treatment was generally well tolerated, with 9 patients (18.8%) experiencing grade >= 3 cytokine release syndrome. Grade 3 to 4 neurotoxic events, which developed in 11 patients (22.9%), were associated with a higher preinfusion disease burden in CNS and were effectively controlled under intensive management. Our results suggest that CD19-specific CAR T cell-based therapy can induce similar high response rates in both BM and CNS diseases. The duration of remission in CNSL was longer than that in BM disease. CD19 CAR T-cell therapy may provide a potential treatment option for previously excluded patients with CNSL, with manageable neurotoxicity.