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多发性骨髓瘤中的双特异性抗体与 CAR-T:患者的适宜选择与序贯治疗

英文原题:Bispecific Antibodies and CAR T in Multiple Myeloma: Appropriate Selection of Patients and Sequencing.

查看英文原题

Bispecific Antibodies and CAR T in Multiple Myeloma: Appropriate Selection of Patients and Sequencing.

PubMed 2025/05/01(内容时间) Mediterr J Hematol Infect Dis Q3 · IF 2.3(JCR 2025)

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中文摘要

T细胞重定向疗法(TCR疗法)推动了复发/难治性多发性骨髓瘤(RRMM)的治疗进展。以嵌合抗原受体(CAR)T细胞和双特异性抗体(BsAb)为代表的药物,在关键临床试验中改善了难治患者预后,并因此进入临床实践。两类策略均通过募集患者自身T细胞靶向特定肿瘤抗原;研究最深入的靶点为B细胞成熟抗原(BCMA)和G蛋白偶联受体C类5成员D(GPRC5D)。

然而,当前获批适应证下的大多数方案,其生存曲线尚未明确出现平台期,这使患者依次接受多种TCR药物成为可能。此外,各药物的毒性谱和给药方式也有所不同。

因此,恰当使用这些药物需要仔细选择适合具体患者的治疗,以最终优化患者结局。在这方面,充分考虑肿瘤和患者特异性特征非常重要。开展定制化临床试验并分析真实世界经验,对于形成循证建议也至关重要。同样,临床前研究对制定可能由免疫学线索和耐药机制认知所驱动的治疗顺序至关重要。本综述旨在为确定最适宜的治疗顺序以及筛选适合各类治疗的患者提供实践指导。

展开英文摘要原文

T-cell redirecting therapies (TCR) marked a step forward in the treatment of relapsed/refractory multiple myeloma (RRMM). These agents, represented by chimeric antigen receptor (CAR) T-cells and bispecific antibodies (BsAbs), proved to ameliorate the prognosis of difficult-to-treat patients in pivotal clinical trials, leading to their introduction into clinical practice. Both strategies rely on recruiting patients' T-cells against specific tumor antigens, with B-cell maturation antigen (BCMA) and G-protein coupled receptor group C family 5 member D (GPRC5D) being the targets most extensively studied. Nevertheless, most of these regimens under the current label do not hesitate in a clear plateau of survival curves, thus raising the scenario of patients receiving more than one TCR agent in sequence.

Also, they differ in their toxicity profiles and administration features. Consequently, the appropriate application of these agents mandates a careful selection of the right treatment for the right patient, with the ultimate intent of optimizing patient outcomes. In this respect, practical considerations regarding tumor- and patient-specific features are of high importance.

Tailored clinical trials and analysis of real-word experiences are also crucial to produce evidence-based recommendations. Likewise, pre-clinical research is critical for the conceptualization of treatment algorithms potentially driven by immunological clues and knowledge of mechanisms of resistance. In this review we aim at providing practical guidance for defining the most appropriate treatment sequencing and determining the selection of patients for each treatment.

论文信息

作者
Puppi M、Sacchetti I、Mancuso K、Tacchetti P、Pantani L、Rizzello I、Iezza M、Talarico M
单位
IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli", Bologna, Italy.Italy
文献类型
综述
期刊
Mediterranean journal of hematology and infectious diseases2025
原文标识
PubMed 40375902 · DOI 10.4084/MJHID.2025.045