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嵌合抗原受体 T 细胞疗法治疗复发或难治性多发性骨髓瘤的疗效和安全性:系统评价和荟萃分析。

Efficacy and Safety of CAR-T Therapy for Relapse or Refractory Multiple Myeloma: A systematic review and meta-analysis.

机构信息

Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.

Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, P.R. China.

出版信息

Int J Med Sci. 2021 Feb 18;18(8):1786-1797. doi: 10.7150/ijms.46811. eCollection 2021.


DOI:10.7150/ijms.46811
PMID:33746596
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7976586/
Abstract

Multiple myeloma (MM) is incurable in spite of recent treatment improvements, highlighting the development of new therapies. Chimeric antigen receptor (CAR) T-cell therapy has dramatically changed the therapeutic effectiveness in high-risk B-cell malignancies. For relapsed/refractory multiple myeloma (RRMM), preclinical evaluations of CAR-T therapy have shown promising efficacy, thus various active clinical trials are under way. Herein, we conducted this review to summarize efficacy and safety of CAR-T therapy and provide more evidence to guide clinical treatments. We systematically searched literature based on databases (PubMed, EMBASE, Cochrane Central Register of Controlled Trials), and conference abstracts reported from American Society of Hematology (ASH), European Hematology Association (EHA) and American Society of Clinical Oncology (ASCO), in addition to other sources (www.clinicaltrials.gov, article citations). Data assessed efficacy and safety of CAR-T therapy in patients with RRMM were extracted and evaluated, and then systematically analyzed by Comprehensive Meta-analysis 3.0 (CMA 3.0). A total of 23 studies including 350 participants from different countries, diagnosed as RRMM and treated with CAR-T therapy (containing 7 antigens targeted by CARs) were combined. In summary, we discovered the pooled overall response rate (77%), complete response rate (37%) and minimal residual disease (MRD) negativity rate within responders (78%). Furthermore, the pooled relapse rate of responders was 38% and median progression-free survival was 8 months. The pooled survival rate was 87% at last follow-up (median, 12 months). In addition, the pooled grade 3-4 rates of cytokine release syndrome (CRS) and neurologic toxicities (NT) were 14% and 13%, respectively. Our study suggests that CAR-T therapy has demonstrated efficacy and safety in RRMM patients. BCMA-targeted CAR-T and anti-BCMA contained regimen have shown better efficacy.

摘要

多发性骨髓瘤(MM)尽管最近的治疗有所改善,但仍无法治愈,这突显了新疗法的发展。嵌合抗原受体(CAR)T 细胞疗法极大地改变了高危 B 细胞恶性肿瘤的治疗效果。对于复发/难治性多发性骨髓瘤(RRMM),CAR-T 治疗的临床前评估显示出了有希望的疗效,因此正在进行各种积极的临床试验。在此,我们进行了这项综述,以总结 CAR-T 疗法的疗效和安全性,并提供更多证据指导临床治疗。我们系统地检索了基于数据库(PubMed、EMBASE、Cochrane 中央对照试验注册)、美国血液学会(ASH)、欧洲血液学协会(EHA)和美国临床肿瘤学会(ASCO)会议摘要以及其他来源(www.clinicaltrials.gov,文章引文)的文献,以评估 RRMM 患者 CAR-T 治疗的疗效和安全性。提取和评估了数据,并通过 Comprehensive Meta-analysis 3.0(CMA 3.0)系统地进行了分析。共有来自不同国家的 350 名 RRMM 患者的 23 项研究接受了 CAR-T 治疗(包含 7 种 CAR 靶向抗原),被合并到一起。总的来说,我们发现了汇总的总体缓解率(77%)、完全缓解率(37%)和应答者中的微小残留病灶(MRD)阴性率(78%)。此外,应答者的复发率为 38%,无进展生存期中位数为 8 个月。最后一次随访(中位数 12 个月)时的总生存率为 87%。此外,细胞因子释放综合征(CRS)和神经毒性(NT)的 3-4 级发生率分别为 14%和 13%。我们的研究表明,CAR-T 疗法在 RRMM 患者中具有疗效和安全性。BCMA 靶向 CAR-T 和含有抗-BCMA 的方案显示出更好的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acd0/7976586/cfe40780073c/ijmsv18p1786g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acd0/7976586/41c88a71d31d/ijmsv18p1786g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acd0/7976586/b45ff4bb0051/ijmsv18p1786g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acd0/7976586/cfe40780073c/ijmsv18p1786g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acd0/7976586/41c88a71d31d/ijmsv18p1786g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acd0/7976586/b45ff4bb0051/ijmsv18p1786g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acd0/7976586/cfe40780073c/ijmsv18p1786g003.jpg

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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
Recent updates on CAR T clinical trials for multiple myeloma.

Mol Cancer. 2019-11-5

[2]
A combination of humanised anti-CD19 and anti-BCMA CAR T cells in patients with relapsed or refractory multiple myeloma: a single-arm, phase 2 trial.

Lancet Haematol. 2019-10

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Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma.

N Engl J Med. 2019-5-2

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Exploratory trial of a biepitopic CAR T-targeting B cell maturation antigen in relapsed/refractory multiple myeloma.

Proc Natl Acad Sci U S A. 2019-4-15

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B cell maturation antigen-specific CAR T cells are clinically active in multiple myeloma.

J Clin Invest. 2019-3-21

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Nat Rev Clin Oncol. 2019-6

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Anti-CD19 CAR T cells with high-dose melphalan and autologous stem cell transplantation for refractory multiple myeloma.

JCI Insight. 2019-2-21

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Biol Blood Marrow Transplant. 2018-12-25

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A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapsed or refractory multiple myeloma.

J Hematol Oncol. 2018-12-20

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