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BCMA 靶向 MRD 检测作为多发性骨髓瘤 BCMA CAR-T 治疗后复发的预测因素

英文原题:BCMA-Directed MRD Detection as a Predictor of Relapse after BCMA CAR T in Multiple Myeloma.

查看英文原题

BCMA-Directed MRD Detection as a Predictor of Relapse after BCMA CAR T in Multiple Myeloma.

PubMed 2024/10/11(内容时间) Clin Lymphoma Myeloma Leuk Q1 · IF 4.1(JCR 2025)

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研究概要

早期 BCMA+ 浆细胞(PC)再次出现可能作为 BCMA CAR-T 治疗后临床复发的预后标志物。

中文摘要

近期获批的CAR-T 细胞和双特异性抗体疗法为复发/难治性多发性骨髓瘤(RRMM)患者带来新希望,临床试验显示其疗效优于标准方案。然而,BCMA靶向治疗后复发较常见,仍需进一步研究。

我们对57例接受BCMA靶向CAR-T 治疗的RRMM患者开展回顾性队列研究。仅纳入CAR-T 输注第30天初始应答后复发、且检测到BCMA表达浆细胞(PC)的患者。按预定时间点采集骨髓样本,采用多色流式细胞术(MFC)检测BCMA阳性浆细胞重新出现情况,并依据国际骨髓瘤工作组标准评估临床应答。

多数患者输注后MFC检测不到BCMA,但随后55%的病例再次出现BCMA阳性浆细胞。值得注意的是,发生临床复发的患者中91%出现BCMA阳性浆细胞重新出现,且往往早于临床复发。早期复发(<6个月)与BCMA较早重新出现相关。

早期出现BCMA阳性浆细胞可能成为BCMA CAR-T 治疗后临床复发的预后标志物。通过MFC监测BCMA阳性浆细胞水平,有望实现早期复发检测并辅助治疗决策。仍需开展进一步研究,包括采用新型BCMA靶向微小残留病(MRD)检测技术,以验证这些发现并优化RRMM管理策略。

展开英文摘要原文

Recent approvals of chimeric antigen receptor T-cells (CAR T) and bispecific antibody therapies offer new hope for relapsed refractory multiple myeloma (RRMM) patients, with superior efficacy over standard regimens observed in clinical trials. However, relapse after BCMA-directed therapy is common and requires further investigation.

We conducted a retrospective cohort study on 57 RRMM patients treated with BCMA-directed CAR T. Only the patients who had an initial response and lost BCMA-expressing identified PC following CAR T infusion at Day 30 were included in the analysis. Multicolor flow cytometry (MFC) to detect BCMA + plasma cell (PC) re-emergence was performed on bone marrow samples at defined intervals and clinical responses were assessed using International Myeloma Working Group criteria.

The majority of patients achieved undetectable BCMA on MFC postinfusion, with subsequent BCMA+ PC re-emergence observed in 55% of cases. Notably, 91% of patients experiencing clinical relapse showed BCMA+ PC re-emergence, often preceding relapse. Early relapse (<6 months) was associated with earlier BCMA re-emergence.

Early BCMA+ PC re-emergence may serve as a prognostic marker for clinical relapse post-BCMA CAR T therapy. Monitoring BCMA+ PC levels via MFC offers potential for early relapse detection and informed treatment decisions. Further studies, including novel BCMA-directed minimal residual disease (MRD) detection technologies, are warranted to validate these findings and refine RRMM management strategies.

论文信息

作者
Rashid A、Wesson W、Abdallah AO、Snyder J、Venkatesh P、Mushtaq MU、Shune L、Witek MA
第一作者单位
Division of Hematologic Malignancies &amp; Cellular Therapeutics, University of Kansas Cancer Center, Westwood, KS; United States Myeloma Innovations Research Collaborative (USMIRC), Westwood, KS.United States
通讯作者单位
Division of Hematologic Malignancies &amp; Cellular Therapeutics, University of Kansas Cancer Center, Westwood, KS; United States Myeloma Innovations Research Collaborative (USMIRC), Westwood, KS. Electronic address: nahmed5@kumc.edu.United States
期刊
Clinical lymphoma, myeloma & leukemia2025 Jan
原文标识
PubMed 39516088 · DOI 10.1016/j.clml.2024.10.003