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接受BCMA嵌合抗原受体T细胞治疗的多发性骨髓瘤患者的早期动力学和反应深度

Early Dynamics and Depth of Response in Multiple Myeloma Patients Treated With BCMA CAR-T Cells.

作者信息

Wong Sandy W, Shah Nina, Ledergor Guy, Martin Thomas, Wolf Jeffrey, Shui Amy M, Huang Chiung-Yu, Martinez-Lopez Joaquin

机构信息

Bone Marrow Transplantation and Hematologic Malignancy Unit, Division of Hematology-Oncology, University of California, San Francisco, San Francisco, CA, United States.

Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, United States.

出版信息

Front Oncol. 2021 Dec 6;11:783703. doi: 10.3389/fonc.2021.783703. eCollection 2021.

Abstract

Chimeric antigen receptor T-cell (CAR-T) therapy targeted against B-cell maturation antigen (BCMA) in multiple myeloma (MM) has produced rapid responses but many eventually relapse. In light of this new treatment, novel predictors of progression-free survival (PFS) are needed. We performed a single institution analysis of 54 BCMA-CAR-T patients. We analyzed patient's overall response rate (ORR) by the IMWG criteria, involved serum-free light chains (iFLC), and minimal residual disease testing by next-generation sequencing (MRD-NGS). Between patients who achieved a ≤SD and those who achieved a ≥PR, PFS differed significantly ( < 0.0001); though there was no difference between patients who achieved a ≥CR . VGPR/PR ( = 0.2). In contrast, patients who achieved a nonelevated iFLC at 15 days ( < 0.0001, HR = 6.8; 95% CI, 2.7-17.3) or 30 days ( < 0.001, HR = 16.7; 95% CI, 3.9-71.7) had a prolonged PFS compared with those with an elevated iFLC. Patients achieving MRD-NGS less than the detectable limit at a sensitivity of 10 had a better PFS than those with detectable disease at 1 month ( = 0.02) and 3 months ( = 0.02). In conclusion, achieving a nonelevated iFLC and an undetectable MRD-NGS quickly were factors that were strongly associated with improved PFS. Further studies are needed to confirm the role of these markers in MM patients receiving CAR-T therapies.

摘要

靶向多发性骨髓瘤(MM)中B细胞成熟抗原(BCMA)的嵌合抗原受体T细胞(CAR-T)疗法已产生快速反应,但许多患者最终复发。鉴于这种新疗法,需要无进展生存期(PFS)的新预测指标。我们对54例接受BCMA-CAR-T治疗的患者进行了单机构分析。我们根据国际骨髓瘤工作组(IMWG)标准分析了患者的总缓解率(ORR)、涉及的游离轻链(iFLC)以及通过下一代测序(MRD-NGS)进行的微小残留病检测。在达到≤疾病稳定(SD)的患者和达到≥部分缓解(PR)的患者之间,PFS有显著差异(P<0.0001);而在达到≥完全缓解(CR)、非常好的部分缓解(VGPR)/PR的患者之间没有差异(P = 0.2)。相比之下,在15天(P<0.0001,HR = 6.8;95%CI,2.7 - 17.3)或30天(P<0.001,HR = 16.7;95%CI,3.9 - 71.7)时iFLC未升高的患者与iFLC升高的患者相比,PFS延长。在灵敏度为10时达到MRD-NGS低于检测限的患者比在1个月(P = 0.02)和3个月(P = 0.02)时疾病可检测的患者具有更好的PFS。总之,快速实现iFLC未升高和MRD-NGS不可检测是与改善PFS密切相关的因素。需要进一步研究来证实这些标志物在接受CAR-T治疗的MM患者中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f178/8685203/1e6198e79043/fonc-11-783703-g001.jpg

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