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重塑多发性骨髓瘤治疗:近期突破

英文原题:Reshaping multiple myeloma treatment: recent breakthroughs.

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Reshaping multiple myeloma treatment: recent breakthroughs.

PubMed 2025/12/25(内容时间) Expert Opin Pharmacother Q2 · IF 3.4(JCR 2025)

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研究概要

这些进展支持向个性化策略转变,旨在实现深度缓解、降低毒性,并在选定患者中接近功能性治愈。

研究思路结论见上方概要

多发性骨髓瘤(MM)的治疗格局正通过免疫治疗策略的进步而迅速演变。双特异性抗体(BsAbs)、CAR-T 细胞疗法以及新兴的三特异性抗体(TsAbs)正在重塑治疗预期,即使在经过多线治疗的患者中也能实现深度且持久的缓解。涵盖领域:现成可用的BsAbs如teclistamab、elranatamab和talquetamab在三类暴露患者中显示出强劲活性,更早期的使用和联合方案进一步增强了缓解深度。然而,挑战依然存在,包括T细胞耗竭、感染风险、低丙种球蛋白血症,以及与递增给药和细胞因子释放综合征相关的后勤问题。CAR-T 疗法,特别是idecabtagene vicleucel和ciltacabtagene autoleucel,实现了高缓解率和快速MRD转阴,但更广泛的应用受到生产时间、毒性管理以及抗原丢失等复发机制的限制。双靶点CAR-T、装甲化构建体和异体平台等创新旨在提高持久性并扩大可及性。MRD评估已成为指导治疗强度和持续时间的生物标志物。与此同时,精细化的风险分层——尤其是针对高危细胞遗传学、功能性和髓外病变——有助于识别可能从早期整合免疫治疗中获益的患者。

展开英文摘要原文

INTRODUCTION: The therapeutic landscape of multiple myeloma (MM) is rapidly evolving through advances in immune-based strategies. Bispecific antibodies (BsAbs), chimeric antigen receptor T-cell (CAR-T) therapies, and emerging trispecific antibodies (TsAbs) are reshaping expectations by delivering deep and durable responses even in heavily pretreated disease.

AREAS COVERED: Off-the-shelf BsAbs such as teclistamab, elranatamab, and talquetamab show robust activity in triple-class - exposed patients, with earlier use and combination regimens further enhancing response depth.

However, challenges remain, including T-cell exhaustion, infection risk, hypogammaglobulinemia, and logistical issues related to step-up dosing and cytokine release syndrome. CAR-T therapies, particularly idecabtagene vicleucel and ciltacabtagene autoleucel, achieve high response rates and rapid MRD negativity, but wider use is limited by manufacturing time, toxicity management, and relapse mechanisms such as antigen loss. Innovations including dual-target CAR-T, armored constructs, and allogeneic platforms aim to improve durability and expand access.

MRD assessment has become a biomarker guiding treatment intensity, and duration. In parallel, refined risk stratification -especially for high-risk cytogenetic, functional, and extramedullary disease- helps identify patients who may benefit from early integration of immunotherapies. EXPERT OPINION: Overall, these advances support a shift toward personalized strategy designed to achieve deep remission, reduce toxicity, and approach functional cure in selected patients.

论文信息

作者
Martino EA、Caserta S、Vigna E、Bruzzese A、Mendicino F、Alvaro ME、Labanca C、Lucia E
单位
Hematology Unit, Department of Onco-Hematology, AO of Cosenza, Cosenza, Italy.Italy
文献类型
综述
期刊
Expert opinion on pharmacotherapy2025 Dec
原文标识
PubMed 41445092 · DOI 10.1080/14656566.2025.2610373