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SOHO 最新进展及未来展望:CAR-T 是否将取代 ASCT 用于 NDMM。

SOHO State of the Art Updates and Next Questions: Will CAR-T Replace ASCT in NDMM.

机构信息

Department of Medicine, Hematology Oncology Fellowship Program, MSKCC, New York, NY.

Department of Medicine, Myeloma Service, MSKCC, New York, NY.

出版信息

Clin Lymphoma Myeloma Leuk. 2024 May;24(5):277-284. doi: 10.1016/j.clml.2024.01.001. Epub 2024 Jan 19.

DOI:10.1016/j.clml.2024.01.001
PMID:38331676
Abstract

The treatment landscape for multiple myeloma (MM) has rapidly evolved over the last 2 decades. The development of triplet and quadruplet regimens including proteasome inhibitors (PI), immunomodulatory agents (IMiDs), and anti-CD38 monoclonal antibodies has dramatically extended overall survival. In addition to effective multidrug regimens, autologous stem cell transplant (ASCT) is a cornerstone of management in newly diagnosed multiple myeloma (NDMM). However, despite these combined treatment modalities, curative therapy for MM remains elusive. Recent, novel immunotherapies including chimeric antigen T-cell (CAR-T) therapy have demonstrated deep and durable responses in relapsed and refractory multiple myeloma (RRMM). Currently 2 CAR-T products, ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel), are approved by the FDA for the treatment of RRMM. The success of CAR-T therapy revolutionized the management of RRMM prompting clinical trials studying CAR-T therapy in the first line setting. The ongoing KarMMa-4, CARTITUDE-5, and CARTITUDE-6 clinical trials may establish CAR-T therapy as a first line option potentially supplanting ASCT in the initial treatment of NDMM. In this review, we discuss the current standard of care management of NDMM, trace the evolution of CAR-T clinical trials in RRMM, and survey ongoing clinical trials studying CAR-T therapy in NDMM.

摘要

在过去的 20 年中,多发性骨髓瘤(MM)的治疗格局迅速发展。三联和四联方案的开发包括蛋白酶体抑制剂(PI)、免疫调节剂(IMiD)和抗 CD38 单克隆抗体,大大延长了总生存期。除了有效的多药方案外,自体干细胞移植(ASCT)是新诊断多发性骨髓瘤(NDMM)管理的基石。然而,尽管采用了这些联合治疗方法,MM 的治愈疗法仍然难以实现。最近,新型免疫疗法包括嵌合抗原 T 细胞(CAR-T)疗法在复发和难治性多发性骨髓瘤(RRMM)中显示出深度和持久的反应。目前,2 种 CAR-T 产品,cilta-cel 和 ide-cel,已获得 FDA 批准用于治疗 RRMM。CAR-T 疗法的成功彻底改变了 RRMM 的治疗管理,促使临床试验研究 CAR-T 疗法在一线治疗中的应用。正在进行的 KarMMa-4、CARTITUDE-5 和 CARTITUDE-6 临床试验可能将 CAR-T 疗法确立为一线选择,有可能在 NDMM 的初始治疗中取代 ASCT。在这篇综述中,我们讨论了 NDMM 的当前标准治疗管理,追溯了 RRMM 中 CAR-T 临床试验的发展,并调查了正在进行的研究 CAR-T 疗法在 NDMM 中的临床试验。

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