Efficacy and safety of CAR19/22 T-cell cocktail therapy in patients with refractory/relapsed B-cell malignancies
Efficacy and safety of CAR19/22 T-cell cocktail therapy in patients with refractory/relapsed B-cell malignancies
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CAR19/22 T 细胞鸡尾酒疗法对难治性/复发性 B 细胞恶性肿瘤患者的疗效和安全性
DOI：
10.1182/blood.2019000017
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发表时间：
2020-01-02
期刊：
影响因子：
20.3
通讯作者：
Huang, Liang
中科院分区：
文献类型：
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作者：
Wang, Na;Hu, Xuelian;Huang, Liang
抗原逃逸复发已成为CD19导向疗法后长期疾病控制的一项重大挑战，针对此，同时靶向CD19和CD22已被提议作为一种潜在的解决方案。从2016年3月至2018年1月，我们对89名患有难治性/复发性B细胞恶性肿瘤的患者进行了一项初步研究，以评估依次输注抗CD19和抗CD22（一种由两种单特异性第三代嵌合抗原受体工程化（CAR19/22）T细胞组成的混合制剂）的疗效和安全性。在51名急性淋巴细胞白血病患者中，微小残留病阴性反应率为96.0%（95%置信区间[CI]，86.3 - 99.5）。中位随访时间为16.7个月（范围，1.3 - 33.3个月），中位无进展生存期（PFS）为13.6个月（95%CI，6.5 - 未达到[NR]），中位总生存期（OS）为31.0个月（95%CI，10.6 - NR）。在38名非霍奇金淋巴瘤患者中，总缓解率为72.2%（95%CI，54.8 - 85.8），完全缓解率为50.0%（95%CI，32.9 - 67.1）。中位随访时间为14.4个月（范围，0.4 - 27.4个月），中位PFS为9.9个月（95%CI，3.3 - NR），中位OS为18.0个月（95%CI，6.1 - NR）。在随访期间有1名患者出现抗原丢失复发。22.4%的患者发生高级别细胞因子释放综合征，1.12%的患者发生神经毒性。除1名患者外，所有这些不良反应都是可逆的。我们的研究结果表明，依次输注CAR19/22 T细胞是安全有效的，并且可能降低了B细胞恶性肿瘤中抗原逃逸复发的比率。
Antigen escape relapse has emerged as a major challenge for long-term disease control post CD19-directed therapies, to which dual-targeting of CD19 and CD22 has been proposed as a potential solution. Between March 2016 and January 2018, we conducted a pilot study in 89 patients, who had refractory/relapsed B-cell malignancies, to evaluate the efficacy and safety of sequential infusion of anti-CD19 and anti-CD22, two single-specific, third-generation chimeric antigen receptor-engineered (CAR19/22) T-cell "cocktail". Among the 51 patients with acute lymphoblastic leukemia, the minimal residual disease-negative response rate was 96.0% (95% confidence interval (CI), 86.3 to 99.5). With a median follow-up of 16.7 months (range, 1.3 to 33.3), the median progression-free survival (PFS) was 13.6 months (95% CI, 6.5 to not reached, NR), and the median overall survival (OS) was 31.0 months (95% CI, 10.6 to NR). Among the 38 patients with non-Hodgkin lymphoma, the overall response rate was 72.2% (95% CI, 54.8 to 85.8), with a complete response rate of 50.0% (95% CI, 32.9 to 67.1). With a median follow-up of 14.4 months (range, 0.4 to 27.4), the median PFS was 9.9 months (95% CI, 3.3 to NR), and the median OS was 18.0 months (95% CI, 6.1 to NR). Antigen loss relapse occurred in one patient during follow-up. High-grade cytokine release syndrome and neurotoxicity occurred in 22.4% and 1.12% patients, respectively. All except one were reversible. Our results indicated that sequential infusion of CAR19/22 T-cell was safe, efficacious, and may have reduced the rate of antigen escape relapse in B-cell malignancies. ChiCTR, number ChiCTR-OPN-16008526.