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双特异性抗体和嵌合抗原受体T细胞疗法在多发性骨髓瘤中的应用:患者的合理选择与治疗顺序

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

作者信息

Puppi M, Sacchetti I, Mancuso K, Tacchetti P, Pantani L, Rizzello I, Iezza M, Talarico M, Manzato E, Masci S, Restuccia R, Barbato S, Armuzzi S, Taurisano B, Vigliotta I, Zamagni E

机构信息

IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli", Bologna, Italy.

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.

出版信息

Mediterr J Hematol Infect Dis. 2025 May 1;17(1):e2025045. doi: 10.4084/MJHID.2025.045. eCollection 2025.

Abstract

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.

摘要

T细胞重定向疗法(TCR)在复发/难治性多发性骨髓瘤(RRMM)的治疗方面向前迈进了一步。这些药物以嵌合抗原受体(CAR)T细胞和双特异性抗体(BsAb)为代表,在关键临床试验中被证明可改善难治性患者的预后,从而被引入临床实践。这两种策略都依赖于募集患者针对特定肿瘤抗原的T细胞,其中B细胞成熟抗原(BCMA)和G蛋白偶联受体C族第5成员D(GPRC5D)是研究最广泛的靶点。然而,目前标签下的大多数这些方案在生存曲线方面并未出现明显的平台期,因此出现了患者依次接受不止一种TCR药物治疗的情况。此外,它们在毒性特征和给药特点方面也有所不同。因此,这些药物的恰当应用要求为合适的患者精心选择正确的治疗方法,最终目的是优化患者的治疗结果。在这方面,考虑肿瘤和患者的特定特征具有重要意义。量身定制的临床试验和对真实世界经验的分析对于产生基于证据的建议也至关重要。同样,临床前研究对于由免疫线索和耐药机制知识驱动的治疗算法的概念化至关重要。在本综述中,我们旨在为确定最合适的治疗顺序以及为每种治疗选择患者提供实用指导。

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