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输注针对CD19和B细胞成熟抗原双靶点的嵌合抗原受体T细胞用于治疗难治性多发性骨髓瘤。

Infusion of chimeric antigen receptor T cells against dual targets of CD19 and B-cell maturation antigen for the treatment of refractory multiple myeloma.

作者信息

Tang Fang, Lu Yin, Ge Yongqin, Shang Jingjing, Zhu Xiaming

机构信息

Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.

出版信息

J Int Med Res. 2020 Jan;48(1):300060519893496. doi: 10.1177/0300060519893496.

Abstract

OBJECTIVE

To investigate the safety and efficacy of chimeric antigen receptor T (CAR-T) cell infusion in patients with refractory multiple myeloma (MM).

METHODS

Sixteen patients diagnosed with refractory MM were included in this study. Patients received initial infusions of T-derived CD19/B-cell maturation antigen (BCMA) CAR-T cells with 100% CD19, followed by second infusions with 40% BCMA and third infusions with 60% BCMA. The total doses were 0.5–1 × 10/kg CD19 and 1.2 − 6.2 × 10/kg BCMA. Patients were monitored after infusion. Levels of interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor-α, and C-reactive protein were determined by enzyme-linked immunosorbent assay.

RESULTS

Cytokine release syndrome (CRS) was observed in all 16 patients. Thirteen patients with CRS stage II−IV had persistent hyperthermia from 5−14 days after infusion, while most patients developed hyperthermia from 1 day after infusion and their temperatures returned to normal within 2−10 days. Levels of all factors were significantly elevated 2 days after infusion, peaked at 5 days, and then gradually decreased to normal levels. All inflammatory factors showed normal levels by 10 days after infusion.

CONCLUSION

Body temperature and levels of inflammatory factors all increased dramatically after infusion of CD19/BCMA CAR-T cells, but recovered to normal levels after appropriate treatment and nursing.

摘要

目的

探讨嵌合抗原受体T(CAR-T)细胞输注治疗难治性多发性骨髓瘤(MM)患者的安全性和有效性。

方法

本研究纳入16例诊断为难治性MM的患者。患者首先输注100% CD19的T细胞来源的CD19/ B细胞成熟抗原(BCMA)CAR-T细胞,随后第二次输注40% BCMA的CAR-T细胞,第三次输注60% BCMA的CAR-T细胞。总剂量为0.5 - 1×10/kg CD19和1.2 - 6.2×10/kg BCMA。输注后对患者进行监测。采用酶联免疫吸附测定法测定白细胞介素(IL)-2、IL-6、IL-10、肿瘤坏死因子-α和C反应蛋白的水平。

结果

16例患者均观察到细胞因子释放综合征(CRS)。13例II-IV级CRS患者在输注后5 - 14天持续高热,而大多数患者在输注后1天出现高热,体温在2 - 10天内恢复正常。所有因子水平在输注后2天显著升高,在5天达到峰值,然后逐渐降至正常水平。输注后10天时所有炎症因子水平均恢复正常。

结论

输注CD19/BCMA CAR-T细胞后体温和炎症因子水平均显著升高,但经过适当治疗和护理后恢复至正常水平。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a0/7114292/06535aa88a39/10.1177_0300060519893496-fig1.jpg

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