决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Historical Perspective of Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma.
Historical Perspective of Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma.
本综述分析现有文献,以更好地了解 allo-SCT 在多发性骨髓瘤管理中的安全性、疗效及当前作用。
背景:多发性骨髓瘤(MM)新疗法的发展改善了患者结局,也减少了异基因干细胞移植(allo-SCT)的使用。现行指南不再支持将allo-SCT作为新诊断MM患者的巩固治疗,即便患者属于高危组。 摘要:目前,allo-SCT通常仅在临床试验中考虑用于年轻的高危复发或难治性MM(RRMM)患者。尽管历史上曾使用该疗法,其获益尚未得到证实。CAR-T细胞疗法和双特异性抗体在治疗对三类或五类药物暴露后仍耐药的MM方面显示出前景,但复发仍常见,患者生存率较低。BCMA靶向治疗及其他新型T细胞靶向疗法之后进行allo-SCT的疗效尚不明确。对于接受这些疗法后复发且符合移植条件的患者,或无法获得这些疗法的患者,allo-SCT可能是一种可行选择。减低强度预处理方案的进展降低了毒性和移植相关(TR)并发症、移植物抗宿主病(GvHD)及移植相关死亡率。扩大单倍体相合等替代供者的使用后,疗效也达到相近水平。移植后GvHD治疗方案和预防复发的维持策略已有改进。 核心信息:本综述分析现有文献,以更好理解allo-SCT在MM治疗中的安全性、疗效和当前作用。由于无法推荐常规使用allo-SCT,仍需开发更新的治疗方案。
BACKGROUND: Advances in novel therapies have improved outcomes for multiple myeloma (MM) patients and the use of allo-SCT has decreased. Current guidelines no longer support allo-SCT as consolidation therapy for newly diagnosed MM, even in high-risk cases. SUMMARY: Allo-SCT is now typically considered only within clinical trials for young, high-risk patients with relapsed or refractory MM (RRMM). It has not proven favorable despite its historical use. CAR T-cell therapy and bispecific antibodies have shown promise in treating triple- and penta-exposed/refractory MM, yet relapse remains common with poor survival rates. The efficacy of allo-SCT following BCMA-directed therapy and other new T-cell-directed therapies is unclear. Allo-SCT might be a viable option for eligible patients who relapse after these therapies, or where such options are unavailable. Advancements in reduced-intensity conditioning regimens have led to lower toxicity and transplant-related (TR) morbidity, lower graft-versus-host disease (GvHD), and TR mortality. Expanded use of alternative donors, like haploidentical donors, has yielded comparable outcomes. Better post-transplant GvHD regimens and maintenance strategies to prevent relapse have been developed. KEY MESSAGES: This review analyzes available literature to better understand the safety, efficacy, and current role of allo-SCT in managing MM. Newer regimens are needed as routine use of allo-SCT cannot be recommended.
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