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超越缓解:多发性骨髓瘤 CAR-T 治疗后的风险适应维持治疗与机制指导的挽救治疗

英文原题:Beyond Remission: Risk-Adapted Maintenance and Mechanism-Guided Salvage After CAR T-Cell Therapy for Multiple Myeloma.

PubMed 2026/09/02(内容时间) Stem Cell Rev Rep Q2 · IF 4.9(JCR 2025)

研究概要

对于持续性 MRD 阴性、无髓外疾病且免疫功能正在恢复的许多患者,结构化观察是合适的。持续性或升高的 MRD、残留病灶、侵袭性疾病生物学特征或不利的 CAR T 细胞动力学,应促使尽早转介临床试验,而非自动进行慢性治疗。挽救治疗可能涉及 BCMA 再靶向、转换为 GPRC5D 或 FcRH5、常规减瘤、放疗、抗体-药物偶联物、双特异性抗体或第二种细胞平台。未来试验应评估无进展生存期,同时评估无感染生存期、无治疗间期、免疫恢复、生活质量以及对后续挽救治疗的反应性。

研究思路结论见上方概要

靶向 B 细胞成熟抗原 (BCMA) 的嵌合抗原受体 (CAR) T 细胞治疗可在复发或难治性多发性骨髓瘤中诱导深度缓解,但复发仍很常见。无论是输注后维持治疗,还是 CAR T 细胞治疗失败后的挽救治疗,均尚无既定标准。 正文:本综述将关键试验、真实世界队列和转化研究综合为用于纵向诊疗的风险适应框架。复发生物学、靶点调节、CAR T 细胞持久性、免疫重建、可测量残留病 (MRD) 和影像学被整合,用于指导结构化观察、限时维持治疗、抢先干预和挽救治疗。仅当残留病带来的估计风险超过感染、血细胞减少和免疫恢复延迟的竞争风险时,预防性治疗才具有合理性。在复发时,治疗选择应首先考虑临床进展速度、疾病累及部位、BCMA、G 蛋白偶联受体 C 类第 5 组成员 D (GPRC5D) 和 Fc 受体同源物 5 (FcRH5) 的当前表达、既往靶点压力以及宿主免疫适应度。

展开英文摘要原文

BACKGROUND: B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy can induce deep responses in relapsed or refractory multiple myeloma, yet relapse remains frequent. Neither post-infusion maintenance nor salvage after CAR T-cell failure has an established standard. MAIN TEXT: This review synthesizes pivotal trials, real-world cohorts, and translational studies into a risk-adapted framework for longitudinal care. Relapse biology, target modulation, CAR T-cell persistence, immune reconstitution, measurable residual disease (MRD), and imaging are integrated to guide structured observation, time-limited maintenance, pre-emptive intervention, and salvage. Preventive treatment is defensible only when the estimated risk posed by residual disease exceeds the competing risks of infection, cytopenia, and delayed immune recovery. At relapse, treatment selection should begin with clinical tempo, disease compartment, contemporary expression of BCMA, G protein-coupled receptor class C group 5 member D (GPRC5D), and Fc receptor-homolog 5 (FcRH5), prior target pressure, and host immune fitness. CONCLUSIONS: Structured observation is appropriate for many patients with sustained MRD negativity, no extramedullary disease, and recovering immune function. Persistent or rising MRD, residual lesions, aggressive disease biology, or unfavorable CAR T-cell kinetics should prompt early trial referral rather than automatic chronic therapy. Salvage may involve BCMA retargeting, a switch to GPRC5D or FcRH5, conventional cytoreduction, radiotherapy, antibody-drug conjugates, bispecific antibodies, or a second cellular platform. Future trials should assess progression-free survival together with infection-free survival, treatment-free interval, immune recovery, quality of life, and responsiveness to subsequent salvage.

论文信息

作者
Su S、Yan S、Wu J、Xiao Y
第一作者单位
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.China
通讯作者单位
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. yixiao@tjh.tjmu.edu.cn.China
文献类型
综述
期刊
Stem cell reviews and reports2026 Sep 2
原文标识
PubMed 42684629 · DOI 10.1007/s12015-026-11228-z