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多发性骨髓瘤中的 CAR-T 细胞治疗:当前数据及临床实践意义的综合综述

英文原题:Chimeric antigen receptor T-cell therapy in multiple myeloma: A comprehensive review of current data and implications for clinical practice.

查看英文原题

Chimeric antigen receptor T-cell therapy in multiple myeloma: A comprehensive review of current data and implications for clinical practice.

PubMed 2023/01/10(内容时间) CA Cancer J Clin Q1 · IF 685.2(JCR 2025)

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中文摘要

多发性骨髓瘤(MM)是一种血液系统恶性肿瘤,其特征为转化浆细胞的克隆性增殖。尽管MM的治疗模式取得了巨大进展,但对大多数患者而言,治愈仍然难以实现。虽然大量患者可以实现长期疾病控制,但肿瘤耐药性的产生导致疾病复发,尤其是在三药难治性MM患者中(定义为对免疫调节剂、蛋白酶体抑制剂和单克隆抗体耐药)。这些患者存在未满足的有效治疗选择需求。嵌合抗原受体(CAR)T细胞疗法是一种新方法,在复发难治性MM(RRMM)的治疗中已显示出有前景的疗效。这些基因修饰的细胞疗法在其他B细胞恶性肿瘤中已显示出深度且持久的缓解,目前的研究旨在在RRMM患者中取得类似结果。早期研究已证明CAR-T 细胞疗法在RRMM中具有显著的缓解率;然而,CAR-T 细胞疗法在骨髓瘤中的持久缓解尚未实现。在这篇综合综述中,作者描述了CAR-T 细胞疗法在骨髓瘤中的发展、重要临床试验的结果、CAR-T 细胞疗法的毒性和局限性,以及克服CAR-T 细胞治疗挑战的策略,以期实现多发性骨髓瘤的治愈。

展开英文摘要原文

Multiple myeloma (MM) is a hematologic malignancy defined by the clonal proliferation of transformed plasma cells. Despite tremendous advances in the treatment paradigm of MM, a cure remains elusive for most patients. Although long-term disease control can be achieved in a very large number of patients, the acquisition of tumor resistance leads to disease relapse, especially in patients with triple-class refractory MM (defined as resistance to immunomodulatory agents, proteosome inhibitors, and monoclonal antibodies). There is an unmet need for effective treatment options in these patients. Chimeric antigen receptor (CAR) T-cell therapy is a novel approach that has demonstrated promising efficacy in the treatment of relapsed, refractory MM (RRMM).

These genetically modified cellular therapies have demonstrated deep and durable remissions in other B-cell malignancies, and current efforts aim to achieve similar results in patients with RRMM. Early studies have demonstrated remarkable response rates with CAR T-cell therapy in RRMM; however, durable responses with CAR T-cell therapies in myeloma have yet to be realized.

In this comprehensive review, the authors describe the development of CAR T-cell therapies in myeloma, the outcomes of notable clinical trials, the toxicities and limitations of CAR T-cell therapies, and the strategies to overcome therapeutic challenges of CAR T cells in the hope of achieving a cure for multiple myeloma.

论文信息

作者
Parikh RH、Lonial S
单位
Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia, USA.United States
文献类型
综述 · 非美国政府资助研究
期刊
CA: a cancer journal for clinicians2023 May-Jun
原文标识
PubMed 36627265 · DOI 10.3322/caac.21771