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血清可溶性 BCMA 可用于监测嵌合抗原受体 T 细胞免疫疗法后多发性骨髓瘤患者的复发。

Serum soluble BCMA can be used to monitor relapse of multiple myeloma patients after chimeric antigen receptor T-cell immunotherapy.

机构信息

Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Nanjing Legend Biotech Inc., Nanjing, China.

出版信息

Curr Res Transl Med. 2023 Apr-Jun;71(2):103378. doi: 10.1016/j.retram.2023.103378. Epub 2023 Jan 12.

Abstract

PURPOSE

Chimeric antigen receptor T-cell (CAR-T) therapy has been proven very effective in treating hematologic malignancies. Ciltacabtagene autoleucel (cilta-cel), a second-generation CAR-T cell with double B cell maturation antigen (BCMA) targeting binding domains, showed an 88% overall response rate (ORR) in patients with relapsed/refractory multiple myeloma (MM), which were carried out in our institute. This study aimed to assess the prognostic potential of soluble BCMA (sBCMA) in serum as a biomarker in MM after CAR-T therapy.

PATIENTS AND METHODS

Serum samples (n = 44) from MM patients were collected before and after CAR-T therapy. The level of sBCMA was analyzed by enzyme-linked immunosorbent assay (ELISA). Additionally, three patients' long-term longitudinal analysis were performed.

RESULTS

Serum sBCMA level was correlated with the percentage of malignant plasma cells in bone marrow (r = 0.613). After CAR-T infusion, the sBCMA level in serum of MM patients decreased markedly (median: 508,513 pg/mL before CAR-T infusion, 89,198 pg/mL in the first month, 8448 pg/mL in the second months, and 6010 pg/mL in the third month after CAR-T infusion). In patients who obtained objective response (≥ PR), re-elevated sBCMA indicated the possibility of disease recurrence. At a cutoff 69,326.27 pg/mL, sBCMA shows high sensitivity (87.5%) and specificity (88.5%) for identifying relapse of MM after CAR-T therapy.

CONCLUSION

Our results suggested that serum sBCMA level changes in response to the clinical status of MM patients after anti-BCMA CAR-T therapy. Furthermore, sBCMA may be a auxiliary biomarker for disease monitoring in MM patients after CAR-T therapy.

摘要

目的

嵌合抗原受体 T 细胞(CAR-T)疗法已被证明在治疗血液系统恶性肿瘤方面非常有效。cilta-cel(ciltacabtagene autoleucel)是一种具有双 B 细胞成熟抗原(BCMA)靶向结合结构域的第二代 CAR-T 细胞,在我们中心进行的复发/难治性多发性骨髓瘤(MM)患者中,其总体缓解率(ORR)达到 88%。本研究旨在评估 CAR-T 治疗后血清可溶性 BCMA(sBCMA)作为 MM 生物标志物的预后潜力。

方法

收集了 44 例 MM 患者在 CAR-T 治疗前后的血清样本。采用酶联免疫吸附试验(ELISA)分析 sBCMA 水平。此外,对 3 例患者进行了长期纵向分析。

结果

血清 sBCMA 水平与骨髓中恶性浆细胞的百分比相关(r=0.613)。CAR-T 输注后,MM 患者血清 sBCMA 水平显著下降(中位数:CAR-T 输注前 508513pg/ml,输注后 1 个月 89198pg/ml,2 个月 8448pg/ml,3 个月 6010pg/ml)。在获得客观缓解(≥PR)的患者中,sBCMA 再次升高提示疾病复发的可能性。当截断值为 69326.27pg/ml 时,sBCMA 对识别 CAR-T 治疗后 MM 的复发具有较高的敏感性(87.5%)和特异性(88.5%)。

结论

我们的研究结果表明,sBCMA 水平的变化可以反映 MM 患者在接受抗-BCMA CAR-T 治疗后的临床状态。此外,sBCMA 可能是 CAR-T 治疗后 MM 患者疾病监测的辅助生物标志物。

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