Department of Medicine, Hematology Oncology Fellowship Program, MSKCC, New York, NY.
Department of Medicine, Myeloma Service, MSKCC, New York, NY.
Clin Lymphoma Myeloma Leuk. 2024 May;24(5):277-284. doi: 10.1016/j.clml.2024.01.001. Epub 2024 Jan 19.
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.
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。