CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:SOHO State of the Art Updates and Next Questions: Will CAR-T Replace ASCT in NDMM.
SOHO State of the Art Updates and Next Questions: Will CAR-T Replace ASCT in NDMM.
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多发性骨髓瘤(MM)的治疗格局在过去20年中迅速演变。包含蛋白酶体抑制剂(PI)、免疫调节剂(IMiDs)和抗CD38单克隆抗体的三联和四联方案的发展显著延长了总生存期。除有效的多药方案外,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,尽管有这些联合治疗模式,MM的治愈性治疗仍然难以实现。近期,包括嵌合抗原T细胞(CAR-T)疗法在内的新型免疫疗法在复发/难治性多发性骨髓瘤(RRMM)中显示出深度且持久的缓解。目前有2种CAR-T 产品,ciltacabtagene autoleucel(cilta-cel)和idecabtagene vicleucel(ide-cel),已获FDA批准用于治疗RRMM。CAR-T 疗法的成功彻底改变了RRMM的管理,促使临床 trials 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临床试验可能确立CAR-T 疗法作为一线选择,有可能在NDMM的初始治疗中取代ASCT。在这篇综述中,我们讨论NDMM的当前标准治疗管理,追溯RRMM中CAR-T 临床试验的演变,并调查正在进行的在NDMM中研究CAR-T 疗法的临床试验。
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.
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